Macrophages develop from bone marrow precursor cells and serve an important role in the immune system. They are present in almost all tissues of the body, and they directly phagocytose and kill foreign pathogens. In addition, they can activate lymphocytes or other immune cells in the body to indirectly respond to pathogens, and protect tissues and organs from foreign pathogens (32). Macrophages are classified into M1 and M2 types. M1 macrophages, as classically activated macrophages, produce nitric oxide (NO), reactive oxygen species (ROS), inducible NO synthase and a large number of pro-inflammatory cytokines, such as IL-1β, interferon (IFN)-γ and TNF-α, which participate in the positive immune response. M1 macrophages also have a role in phagocytosis and tumor cell killing (33).

By contrast, M2 macrophages, as alternatively activated macrophages, produce a large number of anti-inflammatory cytokines, such as IL-4, IL-10 and IL-13, which suppress the immune response to a certain extent. Tumor cells selectively recruit bone marrow-derived macrophages to differentiate into M2 macrophages, that is, tumor-associated macrophages (34), which promote tumor cell proliferation, neovascularization, invasion and metastasis (35). Adjustment of M1/M2 macrophage polarization is key to improve the effectiveness of antitumor therapy. In an experimental study in mice with non-small cell lung cancer (NSCLC), APS modulates the Notch signaling pathway, promotes the production of IL-6, TNF-α and iNOS cytokines, activates M1 macrophages, inhibits macrophage M2-type polarization, and enhances phagocytosis and tumor cell killing (36). Bioinformatics analysis indicates that APS may remodel the tumor microenvironment (TME) and influence cell-cell interactions, specifically through modulation of macrophage M2 polarization and CD8+ T cell exhaustion, thereby overcoming DDP resistance (37). Li et al (38) reported that APS can increase the proportion of M1 macrophages in hepatocellular carcinoma cell-derived xenograft tumors, reduce macrophage M2-type polarization and inhibit the proliferation of hepatocellular carcinoma tumor cells. Furthermore, APS improves the energy metabolism of mouse macrophages in vivo, and enhances the phagocytic activity of RAW 264.7 monocyte macrophages and the immune response in mice (39,40). Mouse macrophages activated by APS are triggered through the Toll-like receptor (TLR)4-mediated signaling pathway; this activation event results in the upregulation of the levels of phosphorylated (p)-p38, p-ERK1/2 and p-JNK. Concurrently, it induces the degradation of IκB-α and the subsequent translocation of NF-κB. Eventually, these molecular events culminate in the production of TNF-α, IL-6 and NO, thereby exerting an inhibitory effect on the proliferation of mouse tumor cells (41,42). Li et al (43) demonstrated that APS enhances the proliferation and phagocytic functions of mouse macrophages, increases the peripheral blood levels of IL-2, TNF-α and IFN-γ, and improves the ability of macrophages to phagocytose tumor cells and inhibit the proliferation of tumor cells. Therefore, APS may enhance macrophage phagocytosis and tumor cell killing, and inhibit tumor cell proliferation and metastasis by increasing M1 macrophage activity, regulating M1/M2-type macrophage polarization and altering the levels of immune cytokines.

DCs are derived from bone marrow CD34⁺ hematopoietic stem cells and are a specialized class of antigen-presenting cells, which are divided into immature DCs (imDCs), mature DCs (mDCs) and regulatory DCs, in accordance with the different stages of cell differentiation (44). ImDCs capture tumor antigens and are stimulated to differentiate into mature mDCs. The mDCs migrate to draining lymph nodes via lymphatic vessels, where they present the antigens to T cells. They secrete various co-stimulatory molecules such as CD80, CD86, CD40 and CD70, which further activate effector T cells, thereby inducing and maintaining anti-tumor immunity (45,46). Enhancing the function of DCs and promoting T-cell activation in patients with cancer are an effective means of antitumor immunotherapy. APS promotes DC maturation, enhances DC antigen-presenting ability, improves the accuracy of tumor cell killing and inhibits tumor cell proliferation (47). When DCs are induced to mature further, the expression of the DC surface co-radical molecules CD80 and CD86 are enhanced. DCs present antigens to T lymphocytes, T lymphocytes increase IL-12 and IFN-γ secretion, improve antitumor immunity and inhibit the proliferation of tumor cells (48).

APS induces the DC cell surface molecule CD80, CD86 and IL-12 expression through the TLR2/4 receptor-mediated MyD88 signaling pathway, increases T lymphocyte activity, releases more IL-2 and enhances antitumor ability (49,50). APS nanoparticles have been shown to modulate the TLR-mediated signaling pathway to activate DCs, to increase the expression levels of co-stimulatory molecules on the surface of DCs and enhance their tumor cell antigen-presenting ability. Subsequently, DCs migrate rapidly to lymph nodes, activate the initial T lymphocytes at lymph nodes and inhibit secondary lymph node tumor growth (51). Furthermore, after APS treatment, DCs have been shown to promote the proliferation of CD4⁺ and CD8⁺ T cells in mice with breast cancer, and a DC-based antitumor vaccine can increase the expression levels of CD40, CD80 and CD86 molecules on the surface of DCs, and inhibit the growth and metastasis of breast cancer cells (52). APS induces morphological changes, the expression of activation markers and the upregulation of inflammatory cytokines in human blood monocyte-derived DCs. In addition, APS promotes the activation of blood DC antigen (BDCA)1 and BDCA3 peripheral blood dendritic cells (pBDCs), which results in the proliferative activation of T cells (53). Therefore, APS may induce the activation of DCs, increased the expression levels of co-stimulatory factors on the surface of DCs, and accelerate the maturation of DCs and antigen presentation. Subsequently, this may enhance the proliferation and activation of CD4⁺ and CD8⁺ T cells, and thus the activation of immune function under the stimulation of cytokines, thereby effectively inhibiting the proliferation and metastasis of tumor cells.

MDSCs are a group of heterogeneous cells derived from the bone marrow; the number of MDSCs in the peripheral blood and spleen is small, accounting for only 4% of cells (54). Under pathological conditions, these immature myeloid-derived heterogeneous cells stop differentiating and become immunosuppressive MDSCs (55,56). MDSCs promote tumor cell survival, angiogenesis, and invasion and metastasis to healthy tissues.

APS inhibit MDSC activity, promote MDSC differentiation and reduce MDSC population. The underlying mechanisms represent a current research hotspot in immunotherapy (51). APS suppress MDSC generation and reduce the MDSC population in the spleens of tumor-bearing mice. Concurrently, APS downregulates immunosuppressive cytokines (IL-10, TGF-β) while upregulating pro-inflammatory cytokines (IFN-γ, TNF-α), thereby enhancing overall immune function (57). Ding et al (58) revealed that APS exert a marked regulatory effect on gut microbiota. APS effectively remodels the gut microbiota environment, and elevates the levels of glutamate and creatine metabolites. Notably, glutamate and creatine serve crucial roles in controlling tumor growth. Simultaneously, APS contributes to the reduction in the number of MDSCs. Furthermore, in mice with melanoma, APS has been shown to curtail the immunosuppressive activity of MDSCs, as manifested by decreased expression levels of Arg-1, IL-10 and TGF-β; this series of changes bolsters the cytotoxic capacity of CD8⁺ T cells against tumor cells. Consequently, this previous study demonstrated that the tumor inhibition rate in mice with melanoma was significantly increased, highlighting the potential of APS in antitumor regulation. APS has been reported to effectively reduce the level of myeloid-derived suppressor cells in the peripheral circulation of lung cancer, continuously improve immune function, and increase the overall clinical treatment efficacy (59). As a common malignant tumor, lung cancer has shown an increasing trend in morbidity and mortality in recent years (60). Multi-targeted, low-toxicity Chinese medicines intervene in the ‘pre-metastatic niche’, a potentially effective means of preventing and treating tumor metastasis. APS has been reported to inhibit the formation of the lung pre-metastatic niche and suppress the recruitment of lung MDSCs. Mechanistically, the expression of S1PR1, STAT3 and p-STAT3 in the S1PR1/STAT3 signaling pathway have been shown to be inhibited by APS, which interferes with the S1PR1/STAT3 signaling pathway and inhibits the accumulation of MDSCs in the pre-metastatic niche to achieve antitumor effects (61). Therefore, APS promote the rapid differentiation of MDSCs, reduce the number and activity of MDSCs, influence the release of immune cytokines, enhance immune functions, and inhibit the proliferation and metastasis of tumor cells.

T lymphocytes develop from bone marrow pluripotent stem cells, differentiate and mature under the induction of thymic hormone, and become immunologically active T cells, playing antitumor specific immunity. T lymphocytes are classified into CD4+ T and CD8+ T cells in accordance with their surface molecular types. CD4+ and CD8+ are the two functionally different subpopulations of T lymphocytes. CD4+ T cells are also known as helper T cells, which play a role in assisting the induction of body immunity. Th cells are differentiated into functional subpopulations such as Th1 cells, Th2 cells, and Th17 cells. The main functional subpopulation of CD8+ T cells is cytotoxic T lymphocytes. Th1 cells secrete IL-2 and TNF-α and stimulate the development of cytotoxic T lymphocytes. TNF-α, which stimulates the activation of macrophages and NK cells, also secretes IFN-γ to kill tumor cells. Th2 cells secrete IL-4, IL-6, and IL-10, which assist B lymphocytes to produce specific antibodies and participate in humoral immunity. Under normal circumstances, the number of Th1 and Th2 cells remains relatively balanced. However, in patients with tumor, a transformation from Th1 cells to Th2 cells occurs, which suppresses the body's cellular immunity. APS enhances the expression of Th1 cytokines such as IL-2 and IFN-γ in the spleen tissues of mice with lung cancer through the TLR4/MyD88/NF-κB signaling pathway while reducing the expression of Th2 cytokines, including IL-4 and IL-10. It also regulates the ratio of Th1/Th2 cells, reverses the transformation from Th1 to Th2, improves the immunity of mice with lung cancer, and inhibits the growth of tumor cells (62). APS not only improves the immune organ index in mice with lung cancer, but also increases the ratio of CD4+/CD8+ T cells in mouse serum and enhances cellular immune activity (63,64). APS protects immune organs, regulates the ratio of CD4+/CD8+ T lymphocyte subpopulations, and inhibits the growth of mouse tumors in vivo; APS also activates antitumor immune cells, promotes the tumor microenvironment of anaerobic metabolism, and effectively induced apoptosis in tumor cells (65). APS increases the number of allogeneic T lymphocytes and the expression level of IL-12 and IFN-γ. In addition, cytotoxic T lymphocytes activated by sensitized DCs kill tumor cells (66). APS reverses Th1-to-Th2 conversion, maintains Th1/Th2 cell balance, regulates CD4+/CD8+ T cell ratio and T cell-related cytokine expression, enhances cellular immunity, and inhibits tumor growth.

Tregs are a group of T lymphocytes that can regulate the immune response and maintain immune tolerance. Tumor immunotherapy reduces the number of Tregs, inhibits their cellular activity, maintains immune function of the body and achieves the killing effects against tumor cells. DCs are a key target for Tregs to inhibit the tumor immune response (67), and Tregs interact with tumor-associated CD11c⁺ DCs to reduce the expression of DC co-stimulatory ligands and inhibit T-cell proliferation. Conversely, the clearance of Tregs leads to the restoration of CD11c⁺ DC immunogenicity, co-stimulatory ligand expression and CD8⁺ T-cell activation, which in turn inhibits tumor growth (68).

APS has been reported to reduce the number of Tregs, decrease the expression levels of splenic TGF-β and IL-10, and inhibit the proliferation and metastasis of malignant melanoma tumor cells in mice (69). APS also repairs cytokine imbalance, inhibits forkhead box protein P3 expression, and suppresses Treg activity and function (70). Through the CXCR4/CXCL12 signaling pathway, APS has been shown to inhibit the recruitment of Tregs by stromal cell-derived factor-1, and to attenuate the proliferation and migration of Tregs. Furthermore, APS activates the TLR4-mediated signaling pathway, thereby inhibiting the expression of TGF-β, decreasing the number of Tregs and sustaining the killing effect of immune cells on tumor cells (71). APS significantly enhanced the PBMC proliferation, reduced Treg frequency, decreased anti-inflammatory cytokines including IL-10, TGF-β, and VEGF-A, and increased the pro-inflammatory cytokine IL-6 (72). Therefore, APS may inhibit Treg activity by reducing the number of Tregs and their cytokine secretion, thus restoring and maintaining the normal immune function of T lymphocytes, achieving the killing effect of T cells on tumor cells, and inhibiting tumor growth and metastasis.

NK cells are derived from bone marrow lymphoid stem cells, which are important members of the lymphocyte family, and they are not controlled by high-resolution antigen specificity. NK cells can rapidly recognize and remove heterogeneous cells, and the degree of attenuation in vivo is closely related to the malignant progression of tumors (73). NK cells secrete cytokines, regulate adaptive immunity and kill tumor cells, and they have killing and inhibitory effects on hepatocellular carcinoma, NSCLC, breast cancer and ovarian cancer cells (74–77). APS has been reported to inhibit the proliferation of leukemia cells by activating MHC class I polypeptide-related sequence A molecules on the surface of leukemia cells, and enhances the sensitivity of HL-60 cells to NK cell killing activity and inhibit leukemia cell growth (78). Low-molecular-weight APS can protect the immune organs of mice with hepatocellular carcinoma and stimulate NK cells to kill tumor cells. In addition, APS promotes the proliferation of splenic lymphocytes, increases the activity of NK cells and enhances the immune response of rats with cancer (79,80).

Tumor cell proliferation primarily aggravates cancer progression, and pharmacological intervention in tumor cell proliferation serves an important role in tumor therapy. F-box and WD-40 structural domain protein 7 (FBXW7) is a classical tumor suppressor, the translation of which is inhibited by microRNA (miR)-27a in ovarian cancer cells. APS inhibits the proliferation of ovarian cancer cells through the miR-27a/FBXW7 signaling pathway, revealing the therapeutic potential of APS for ovarian cancer (81). Lung cancer is the second most common and the deadliest type of cancer worldwide. Clinically, non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer (82). APS can inhibit the proliferation and migration of NSCLC cells, and its mechanism of action is related to the regulation of the miR-195-5p signaling pathway; in addition, APS inhibits the lung cancer cell cycle and improves the morphology of lung cancer cells (83,84). APS inhibit TGF-β1-induced epithelial-mesenchymal transition (EMT) in A549/DDP cell xenografts of lung adenocarcinoma, which is associated with inhibition of PI3K/Akt pathway protein activation (85). In a study exploring the synergistic inhibitory effect of APS and cisplatin on the growth of human carcinoma nasopharyngeal cell (CNE), APS was shown to exert an inhibitory effect on the proliferation of nasopharyngeal carcinoma cells in a time- and dose-dependent manner, and the combined application of APS and cisplatin could inhibit the migration and invasion of CNE-1 cells, which was more effective than the use of either drug alone with regard to the antitumor effect of either drug (86). In addition, the study demonstrated that APS at varying concentrations inhibited the proliferation of human colorectal cancer SW620 cells, inducing SW620 cell cycle arrest predominantly at the G2/M phase (87). In addition, APS can markedly inhibit the proliferation and invasion of prostate cancer (PCa) cells in a time- and dose-dependent manner. Under APS treatment, the cellular triacylglycerol and cholesterol levels of patients were revealed to be markedly reduced, and APS can regulate the miR-138-5p/SIRT1/SREBP1 pathway in PCa to inhibit lipid metabolism and tumorigenesis (88). Furthermore, APS enhances the expression of miR-133a in MG63 osteosarcoma cells, inhibits the JNK signaling pathway, the proliferation, migration and invasion of MG63 cells, and induces the apoptosis of MG63 cells (89).

Apoptosis is a type of programmed cell death regulated by various genes, which serves an important role in tumorigenesis and development (90). The occurrence of malignant tumors is due to the uncontrolled and excessive proliferation of tumor cells. In recent years, promoting the apoptosis of tumor cells has become a focus of research for the treatment of tumors. There are two main apoptotic pathways: i) The extrinsic pathway, which is mediated by the activation of caspases through the cell membrane death receptor; and ii) the intrinsic pathway, which is mediated by mitochondria in the cytoplasm that release apoptotic factors and activate caspases. These activated caspases degrade the key proteins in the cell, causing apoptotic cell death. The genes and proteins that have been studied include caspase-3, caspase-8, caspase-9, the Bcl-2 family and cyclooxygenase-2 (91). In the mitochondrion-mediated intrinsic apoptotic pathway, proteins belonging to the Bcl-2 family alter mitochondrial membrane permeability, regulate cytochrome c release and modulate the apoptotic process (92). Bax and Bcl-2 belong to the Bcl-2 superfamily, which are key genes in the regulation of apoptosis, and they are in a balanced state in normal organisms. Notably, apoptosis can be induced by a decrease in the expression levels of the apoptosis inhibitory protein Bcl-2, or an increase in the expression levels of the pro-apoptotic protein Bax (93).

APS markedly promotes the anti-proliferative and apoptotic effects of cisplatin on nasopharyngeal carcinoma cells, by regulating the expression levels of Bax/Bcl-2, caspase-3, and caspase-9 (94). APS also markedly decreases gastric cancer (GC) cell viability, and accelerates GC cell apoptosis in a time- and dose-dependent manner; these effects are associated with an increase in p-AMPK. APS-treated MGC-803 cells have been shown to exhibit the typical morphological features of apoptosis, alongside cell cycle arrest at the S phase (95). A novel cold-water-soluble polysaccharide (APS4) was isolated from Astragalus membranaceus, induce mitochondria-dependent apoptosis, which is associated with intracellular ROS accumulation, mitochondrial membrane potential imbalance, increased pro-apoptotic/anti-apoptotic Bax/Bcl-2 ratio and cytochrome c release (96).

The Notch signaling has an important role in the transformation and proliferation of human malignant tumors, and it is readily activated in human non-small cell lung carcinoma, whereas the inhibitors of Notch signaling can attenuate cell proliferation and induce apoptosis in lung cancer cell lines. APS has been shown to inhibit the expression of Notch1 and Notch3 in NSCLC cell lines to upregulate the pro-apoptotic Bax and caspase 8, promoting apoptosis in NSCLC cell lines (97-101). APS may also inhibit tumor cells of A549, MC38 and B16, induce apoptosis and prevent cell transformation from the G₁ phase to the S phase of the cell cycle, and is associated with the expression of molecules related to immunogenic cell death and the regulation of immune cells (102). APS has also been reported to decrease the number of HepG2 liver cancer cells in S-phase, and cells were arrested at the G0-G1 and G2-M phases, block the cellular proliferation cycle and induce apoptosis in cancer cells (103,104). Wang (105) investigated the role of ERK1/2 in the promotion of apoptosis in HepG2 cells by APS and found that caspase-3 activity is increased, ERK1/2 expression is decreased and APS inhibits the ERK1/2 signaling pathway to promote apoptosis in tumor cells.

Protein O-GlcNAc modification is a unique post-translational modification, and various nuclear and cytoplasmic proteins can be modified by the O-GlcNAcylation of free hydroxyl groups of selected serine and threonine residues (106). The cell modification cycle is mediated by O-GlcNAc transferase, which transfers N-acetylglucosamine to the protein substrate, and the O-GlcNAcase enzyme, which removes this modification from the protein (107–109). O-GlcNAcylation affects a wide range of protein functions, including transcription, subcellular localization, protein-protein interactions and protein stability (110). In numerous types of cancer, O-GlcNAc modification is associated with endoplasmic reticulum (ER) stress, and reduced O-GlcNAcylation leads to the activation of the ER stress response in a variety of cancer cells (111–113). APS promotes doxorubicin (Dox)-induced apoptosis and ER stress response in a dose-dependent manner. In addition, APS decreases O-GlcNAc transferase mRNA levels and protein stability. and increases O-GlcNAcase expression level. APS thus reduces O-GlcNAcylation and promotes Dox-induced apoptosis in hepatocellular carcinoma cells, leading to the exacerbation of ER stress and the activation of apoptotic pathways (114).

Invasion and metastasis are crucial biological characteristics of malignant tumors, as well as important factors contributing to tumor recurrence following surgery. Tumor cells disseminate to new organs and tissues through the blood and lymphatic systems, subsequently proliferating. Notably, tumor vasculature serves as a conduit for metastasizing tumor cells; therefore, inhibiting tumor cell angiogenesis can impede the progressive deterioration of tumors and aid in the treatment of neoplastic diseases. Vascular endothelial growth factor (VEGF) is widely recognized as a pivotal mediator of tumor angiogenesis (115). APS effectively inhibits tumor cell metastasis, with APS efficiently suppressing Lewis lung cancer growth and metastasis in mice while enhancing immune organ function. Moreover, it suppresses the protein expression levels of VEGF and EGFR in tumor tissues, exhibiting a concentration-dependent relationship (116). The NF-κB signaling pathway has a critical role in lung cancer prevention and treatment; APS significantly downregulates NF-κB transcriptional activity, thereby inhibiting the proliferation and metastasis of A549 and NCI-H358 NSCLC cells (117,118). Furthermore, the angiogenesis of human colorectal cancer tumors is markedly inhibited by APS, which is closely associated with the reduction in VEGF expression within tumor tissues (119). APS can inhibit the proliferation and invasion of HS-746T cells, suppress the expression of miR-25 mRNA, and promote the expression of FBXW7 mRNA. It can also reverse the increase in miR-25 and the suppression of FBXW7 caused by transfection with miR-25 mimic. APS can inhibit the proliferation and invasion of gastric cancer HS-746T cells through the miR-25/FBXW7 signaling pathway (120). miR-133, which serves as a tumor suppressor, inhibits proliferation, migration in tumor cells and promotes their apoptosis. APS has been shown to upregulate the expression levels of miR-133a, promote the inactivation of the JNK signal transduction pathway, and inhibit the proliferation, metastasis and invasion of MG63 osteosarcoma cells while inducing apoptosis (89,121). EMT serves a crucial role in tumor migration and invasion. APS can serve as a therapeutic agent for breast cancer by inhibiting the Wnt/β-catenin signaling pathway to reduce proliferation and the EMT-mediated migration and invasion of breast cancer cells (122,123). Moesin (MSN) serves as a potential biomarker associated with tumor invasion and metastasis while maintaining PD-L1 stability. In hepatocellular carcinoma, MSN is targeted by miR-133a-3p, which negatively regulates its expression; notably, APS attenuates PD-L1-mediated immunosuppression by modulating the miR-133a-3p/MSN pathway (124).

Under physiological conditions, free radicals enhance immune function; by contrast, under pathological conditions, free radicals cause damage to normal tissues and cells, leading to diseases (125). Scavenging free radicals is another important tool for tumor prevention and treatment. The activities of free radical-scavenging enzymes, such as catalase and superoxide dismutase (SOD), are markedly decreased in patients with tumors, whereas the content of lipid peroxides and lipid peroxidation products such as malondialdehyde (MDA) are elevated (126). In addition, the anti-oxidative stress function is decreased. APS have been reported to reduce free radical production, increase SOD activity, decrease MDA content, and scavenge ROS and reactive nitrogen species generated by intracellular oxidative stress (127).

In patients with cancer who are receiving chemotherapy, most treatment failures or deaths are attributed to tumor MDR (128). Modern pharmaceutical research focuses on drugs that can reverse or escape MDR, and the key to reversing tumor drug resistance lies in blocking the MDR pathway, reducing drug efflux and improving the chemosensitivity of tumor cells (129). APS markedly increases tumor response to chemotherapeutic drugs and reverses the MDR effect, while reducing the toxicity response induced by chemotherapeutic drugs (130). APS can also inhibit TGF-β1 overexpression-mediated EMT, and inhibit the proliferation of cisplatin-resistant A549 cell xenograft tumors (131). In vitro experiments confirmed that APS induces apoptosis in GC cells and enhances the pro-apoptotic effect of Adriamycin on GC cells, and that APS serves as a chemotherapeutic sensitizer to a certain extent (95). In addition, in the HL-60/A cell line with high drug resistance, APS induces apoptosis, activates the caspase cascade reaction, decreases the expression levels of MDR-associated protein and increases the concentration of intracellular antitumor drugs (132). Furthermore, APS increases the sensitivity of tumor cells to chemotherapeutic drugs, such as apatinib, escapes MDR and strengthens the antitumor effect (133). In the experimental study using H22 hepatoma cell xenograft mouse models, the expression levels of IL-6 and TNF-α were increased, whereas those of IL-10, P-glycoprotein and MDR1 were decreased in the APS treatment group. In addition, APS was shown to enhance the antitumor effect of Adriamycin (134). APS can also serve as a chemosensitive enhancer by activating the JNK signaling pathway and enhancing the sensitivity of SKOV3 ovarian cancer cells to cisplatin (135). Furthermore, APS has been shown to enhance the sensitivity of HeLa cervical cancer cells to cisplatin chemotherapy by upregulating the autophagy-related protein beclin1, promoting the conversion of LC3 I to LC3 II, and downregulating the marker protein p62 to enhance the autophagic activity of HeLa cells (133). APS promotes the apoptosis of gefitinib-resistant cells, and reduces cell proliferation and migration. Moreover, APS inhibits the PD-L1/SREBP-1/EMT signaling pathway, increases the expression levels of E-cadherin, reduces the expression levels of N-cadherin and vimentin, and reverses the acquired resistance of lung cancer cells to gefitinib (136).