Effect of <em>Polygonatum Sibiricum</em> polysaccharides on nude mice model of prostate cancer PC‑3 cells

Liu,Chenxi; Tang,Yuhong; Wang,Jingjing; Zhou,Yan; Yang,Shuaibo; Dong,Shaowen; Zhao,Guobin

doi:10.3892/or.2025.8917

Effect of Polygonatum Sibiricum polysaccharides on nude mice model of prostate cancer PC‑3 cells

Authors:
- Chenxi Liu
- Yuhong Tang
- Jingjing Wang
- Yan Zhou
- Shuaibo Yang
- Shaowen Dong
- Guobin Zhao
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Affiliations: Graduate School, Hebei North University, Zhangjiakou, Hebei 075000, P.R. China, Department of Immunology, Hebei North University, Zhangjiakou, Hebei 075000, P.R. China, Department of Urology, The First Affiliated Hospital of Hebei North University, Zhangjiakou, Hebei 075000, P.R. China
Published online on: May 22, 2025 https://doi.org/10.3892/or.2025.8917
Article Number: 84

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Abstract

The present study aimed to explore the influence of Polygonatum sibiricum polysaccharides (PSP) on the progression of prostate cancer PC‑3 cell xenografts in nude mice, with a specific emphasis on analyzing the regulation of key proteins in the phosphatidylinositol 3‑kinase/protein kinase B (PI3K/Akt) and nuclear factor‑kappa B (NF‑κB) signaling pathways. An androgen‑independent PC‑3 prostate cancer cell line was subcutaneously injected into immunocompromised BALB/c nude mice to establish a xenograft model. The mice were randomly allocated into five groups, each comprising six animals. Drug dosages were determined according to the body surface area ratio between humans and nude mice. The control group was given normal saline, whereas the docetaxel (DTX) group received docetaxel at a dosage of 5 mg/(kg·d). The PSP treatment groups were administered PSP at low [100 mg/(kg x d)], medium [200 mg/(kg x d)], and high [400 mg/(kg x d)] doses. Each treatment was delivered via gavage at a volume of 0.2 ml every other day for a 30‑day period. Tumor volume and body weight were recorded every 3 days to evaluate the effect of PSP on xenograft growth, with tumor size and overall health status serving as the primary assessment criteria. A total of 4 h after drug administration, tumor volume was measured to calculate the tumor inhibition rate. Subsequently, apoptosis in tumor tissues was evaluated using the TUNEL assay. Immunohistochemistry was conducted to detect the expression levels of PI3K, Akt, NF‑κB p65, their phosphorylated forms (p‑PI3K, p‑Akt and p‑NF‑κB p65), and caspase‑3. At the initial stage of establishing the tumor‑bearing nude mouse model of prostate cancer, all groups of nude mice displayed stable mental states, high levels of activity, regular feeding habits and heightened responsiveness to external stimuli. However, as the tumors progressed, a decline in activity, food intake and responsiveness to stimuli was observed across all groups. PSP inhibited the proliferation of PC‑3 cells and induced apoptosis in tumor‑bearing nude mice, presumably by downregulating PI3K, Akt and NF‑κB p65, thereby suppressing the PI3K/Akt and NF‑κB signaling pathways. Simultaneously, PSP upregulated the expression of caspase‑3, which contributed to its antitumor effects in the PC‑3 prostate cancer model.

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1	Oczkowski M, Dziendzikowska K, Pasternak-Winiarska A, Włodarek D and Gromadzka-Ostrowska J: Dietary factors and prostate cancer development, progression, and reduction. Nutrients. 13:4962021. View Article : Google Scholar : PubMed/NCBI
2	Bergengren O, Pekala KR, Matsoukas K, Fainberg J, Mungovan SF, Bratt O, Bray F, Brawley O, Luckenbaugh AN, Mucci L, et al: 2022 Update on prostate cancer epidemiology and risk factors-A systematic review. Eur Urol. 84:191–206. 2023. View Article : Google Scholar : PubMed/NCBI
3	Mumuni S, O'Donnell C and Doody O: The risk factors and screening uptake for prostate cancer: A scoping review. Healthcare (Basel). 11:27802023. View Article : Google Scholar : PubMed/NCBI
4	Chen L, Xu YX, Wang YS, Ren YY, Chen YM, Zheng C, Xie T, Jia YJ and Zhou JL: Integrative Chinese-Western medicine strategy to overcome docetaxel resistance in prostate cancer. J Ethnopharmacol. 331:1182652024. View Article : Google Scholar : PubMed/NCBI
5	Chen XJ, Duan JF, Liu KQ, Guo YY, Wang DP, Liu M, Zhao D, Li B, Li HL and Wang XB: Botany, traditional uses, and pharmacology of polygonati rhizoma. Chin Med Cult. 4:251–259. 2021. View Article : Google Scholar
6	Shen S and Jiang S: Chinese herbal medicines of supplementing Qi and nourishing Yin combined with chemotherapy for non-small cell lung cancer: A meta-analysis and systematic review. J Cell Biochem. 120:8841–8848. 2019. View Article : Google Scholar : PubMed/NCBI
7	Liu Z, Ni H, Yu L, Xu S, Bo R, Qiu T, Gu P, Zhu T, He J, Wusiman A, et al: Adjuvant activities of CTAB-modified Polygonatum sibiricum polysaccharide cubosomes on immune responses to ovalbumin in mice. Int J Biol Macromol. 148:793–801. 2020. View Article : Google Scholar : PubMed/NCBI
8	Yang C, Li D, Ko CN, Wang K and Wang H: Active ingredients of traditional Chinese medicine for enhancing the effect of tumor immunotherapy. Front Immunol. 14:11330502023. View Article : Google Scholar : PubMed/NCBI
9	Xiao X, Guo Z, Li X, Chen P, Li Y, Zhang J, Mao C, Ji D, Su L, Gao B and Lu T: Effects of wine processed Polygonatum polysaccharides on immunomodulatory effects and intestinal microecology in mice. Qual Assur Saf Crops Foods. 15:61–174. 2023.
10	Zhang Q, Yang Z and Su W: Review of studies on polysaccharides, lignins and small molecular compounds from three Polygonatum Mill. (Asparagaceae) spp. in crude and processed states. Int J Biol Macromol. 260:1295112024. View Article : Google Scholar : PubMed/NCBI
11	Pan M, Wu Y, Sun C, Ma H, Ye X and Li X: Polygonati Rhizoma: A review on the extraction, purification, structural characterization, biosynthesis of the main secondary metabolites and anti-aging effects. J Ethnopharmacol. 327:1180022024. View Article : Google Scholar : PubMed/NCBI
12	Gong H, Gan X, Li Y, Chen J, Xu Y, Shi S, Li T, Li B, Wang H and Wang S: Review on the genus Polygonatum polysaccharides: Extraction, purification, structural characteristics and bioactivities. Int J Biol Macromol. 229:909–930. 2023. View Article : Google Scholar : PubMed/NCBI
13	Xie Y, Jiang Z, Yang R, Ye Y, Pei L, Xiong S, Wang S, Wang L and Liu S: Polysaccharide-rich extract from Polygonatum sibiricum protects hematopoiesis in bone marrow suppressed by triple negative breast cancer. Biomed Pharmacother. 137:1113382021. View Article : Google Scholar : PubMed/NCBI
14	Han SY, Hu MH, Qi GY, Ma CX, Wang YY, Ma FL, Tao N and Qin ZH: Polysaccharides from Polygonatum inhibit the proliferation of prostate cancer-associated fibroblasts. Asian Pac J Cancer Prev. 17:3829–3833. 2016.PubMed/NCBI
15	Gao D, Fang L, Liu C, Yang M, Yu X, Wang L, Zhang W, Sun C and Zhuang J: Microenvironmental regulation in tumor progression: Interactions between cancer-associated fibroblasts and immune cells. Biomed Pharmacother. 167:1156222023. View Article : Google Scholar : PubMed/NCBI
16	Siegel RL, Giaquinto AN and Jemal A: Cancer statistics, 2024. CA Cancer J Clin. 74:12–49. 2024. View Article : Google Scholar : PubMed/NCBI
17	Crucitta S, Cucchiara F, Mathijssen R, Mateo J, Jager A, Joosse A, Passaro A, Attili I, Petrini I, van Schaik R, et al: Treatment-driven tumour heterogeneity and drug resistance: Lessons from solid tumours. Cancer Treat Rev. 104:1023402022. View Article : Google Scholar : PubMed/NCBI
18	Cussenot O, Cancel-Tassin G, Rao SR, Woodcock DJ, Lamb AD, Mills IG and Hamdy FC: Aligning germline and somatic mutations in prostate cancer. Are genetics changing practice? BJU Int. 132:472–484. 2023.PubMed/NCBI
19	Wang K, Chen Q, Shao Y, Yin S, Liu C, Liu Y, Wang R, Wang T, Qiu Y and Yu H: Anticancer activities of TCM and their active components against tumor metastasis. Biomed Pharmacother. 133:1110442021. View Article : Google Scholar : PubMed/NCBI
20	Zhang Y, Chen HG, Zhao C, Gong XJ and Zhou X: Research progress on anti-hepatocellular carcinoma mechanism of active ingredients of traditional Chinese medicine. Zhongguo Zhong Yao Za Zhi. 45:3395–3406. 2020.(In Chinese). PubMed/NCBI
21	Qiang M, Cai P, Ao M, Li X, Chen Z and Yu L: Polysaccharides from Chinese materia medica: Perspective towards cancer management. Int J Biol Macromol. 224:496–509. 2023. View Article : Google Scholar : PubMed/NCBI
22	Liu X, Xiao X, Han X, Yao L and Lan W: Natural flavonoids alleviate glioblastoma multiforme by regulating long non-coding RNA. Biomed Pharmacother. 161:1144772023. View Article : Google Scholar : PubMed/NCBI
23	Hu J, Qiu S, Wang F, Li Q, Xiang CL, Di P, Wu Z, Jiang R, Li J, Zeng Z, et al: Functional divergence of CYP76AKs shapes the chemodiversity of abietane-type diterpenoids in genus Salvia. Nat Commun. 14:46962023. View Article : Google Scholar : PubMed/NCBI
24	Cattivelli A, Conte A and Tagliazucchi D: Quercetins, chlorogenic acids and their colon metabolites inhibit colon cancer cell proliferation at physiologically relevant concentrations. Int J Mol Sci. 24:122652023. View Article : Google Scholar : PubMed/NCBI
25	Wu XL, Lin SG, Mao YW, Wu JX, Hu CD, Lv R, Zeng HD, Zhang MH, Lin LZ, Ouyang SS and Zhao YX: Wnt/β-catenin signalling pathway in breast cancer cells and its effect on reversing tumour drug resistance by alkaloids extracted from traditional Chinese medicine. Expert Rev Mol Med. 25:e212023. View Article : Google Scholar : PubMed/NCBI
26	Liu MQ, Bao CJ, Liang XF, Ji XY, Zhao LQ, Yao AN, Guo S, Duan JL, Zhao M and Duan JA: Specific molecular weight of Lycium barbarum polysaccharide for robust breast cancer regression by repolarizing tumor-associated macrophages. Int J Biol Macromol. 261:1296742024. View Article : Google Scholar : PubMed/NCBI
27	Yao Y, Zhou L, Liao W, Chen H, Du Z, Shao C, Wang P and Ding K: HH1-1, a novel Galectin-3 inhibitor, exerts anti-pancreatic cancer activity by blocking Galectin-3/EGFR/AKT/FOXO3 signaling pathway. Carbohydr Polym. 204:111–123. 2019. View Article : Google Scholar : PubMed/NCBI
28	Li Q, Zhang C, Xu G, Shang X, Nan X, Li Y, Liu J, Hong Y, Wang Q and Peng G: Astragalus polysaccharide ameliorates CD8⁺ T cell dysfunction through STAT3/Gal-3/LAG3 pathway in inflammation-induced colorectal cancer. Biomed Pharmacother. 171:1161722024. View Article : Google Scholar : PubMed/NCBI
29	Li W, Zhou Q, Lv B, Li N, Bian X, Chen L, Kong M, Shen Y, Zheng W, Zhang J, et al: Ganoderma lucidum polysaccharide supplementation significantly activates T-cell-mediated antitumor immunity and enhances anti-PD-1 immunotherapy efficacy in colorectal cancer. J Agric Food Chem. 72:12072–12082. 2024. View Article : Google Scholar : PubMed/NCBI
30	Lai W, Ning Q, Wang G, Gao Y, Liao S and Tang S: Antitumor activity of Polygonatum sibiricum polysaccharides. Arch Pharm Res. 47:696–708. 2024. View Article : Google Scholar : PubMed/NCBI
31	Zhao G, Zhou Y, Tang Y, Abbas M, Dong S, Zhao X, Liu X, Wang X, Li C and Liu C: Potential antitumor effect of polysaccharides extracted from Polygonatum sibiricum on human prostate cancer PC-3 cells. Oncol Lett. 29:282024. View Article : Google Scholar : PubMed/NCBI
32	Rezaei S, Nikpanjeh N, Rezaee A, Gholami S, Hashemipour R, Biavarz N, Yousefi F, Tashakori A, Salmani F, Rajabi R, et al: PI3K/Akt signaling in urological cancers: Tumorigenesis function, therapeutic potential, and therapy response regulation. Eur J Pharmacol. 955:1759092023. View Article : Google Scholar : PubMed/NCBI
33	Herberts C, Murtha AJ, Fu S, Wang G, Schönlau E, Xue H, Lin D, Gleave A, Yip S, Angeles A, et al: Activating AKT1 and PIK3CA mutations in metastatic castration-resistant prostate cancer. Eur Urol. 78:834–844. 2020. View Article : Google Scholar : PubMed/NCBI
34	Li Q, Li Z, Luo T and Shi H: Targeting the PI3K/AKT/mTOR and RAF/MEK/ERK pathways for cancer therapy. Mol Biomed. 3:472022. View Article : Google Scholar : PubMed/NCBI
35	Hoxhaj G and Manning BD: The PI3K-AKT network at the interface of oncogenic signalling and cancer metabolism. Nat Rev Cancer. 20:74–88. 2020. View Article : Google Scholar : PubMed/NCBI
36	Zhao J, Ma L, Ni Z and Liu H: In vitro facilitating role of Polygonatum sibiricum polysaccharide in osteogenic differentiation of bone marrow mesenchymal stem cells from patients with multiple myeloma. Biotechnol Lett. 43:1311–1322. 2021. View Article : Google Scholar : PubMed/NCBI
37	Xu Y, Guo Y, Lu C, Yu L, Fang C and Li C: Polygonatum sibiricum polysaccharide inhibited liver cancer in a simulated tumor microenvironment by eliminating TLR4/STAT3 pathway. Biol Pharm Bull. 46:1249–1259. 2023. View Article : Google Scholar : PubMed/NCBI
38	Li L, Thakur K, Cao YY, Liao BY, Zhang JG and Wei ZJ: Anticancerous potential of polysaccharides sequentially extracted from Polygonatum cyrtonema Hua in Human cervical cancer Hela cells. Int J Biol Macromol. 148:843–850. 2020. View Article : Google Scholar : PubMed/NCBI