Cyclovirobuxine D inhibits growth and progression of non‑small cell lung cancer cells by suppressing the KIF11‑CDC25C‑CDK1‑CyclinB1 G<sub>2</sub>/M phase transition regulatory network and the NFκB/JNK signaling pathway

Xue,Ting; Xue,Ting; Chen,Yaodong; Chen,Yaodong; Xu,Jia; Xu,Jia; Du,Weiqin; Du,Weiqin; Kong,Pengzhou; Kong,Pengzhou; Zhang,Xinri; Zhang,Xinri

doi:10.3892/ijo.2023.5505

Cyclovirobuxine D inhibits growth and progression of non‑small cell lung cancer cells by suppressing the KIF11‑CDC25C‑CDK1‑CyclinB1 G₂/M phase transition regulatory network and the NFκB/JNK signaling pathway

Authors:
- Ting Xue
- Yaodong Chen
- Jia Xu
- Weiqin Du
- Pengzhou Kong
- Xinri Zhang
View Affiliations

Affiliations: State Key Laboratory for Pneumoconiosis of National Health Commission, Key Laboratory of Prevention, Treatment and Fundamental Studies for Respiratory Diseases of Shanxi, Department of Respiratory and Critical Care Medicine, First Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China, Department of Ultrasonic Imaging, First Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China, School of Medical Application Technology, Shenyang Medical College, Shenyang, Liaoning 110034, P.R. China, Department of Clinical Laboratory, People's Hospital of Lüliang, Lüliang, Shanxi 033000, P.R. China, Key Laboratory of Cellular Physiology of The Ministry of Education and Department of Pathology, Shanxi Medical University, Yingze, Taiyuan, Shanxi 030001, P.R. China
Published online on: March 15, 2023 https://doi.org/10.3892/ijo.2023.5505
Article Number: 57
Copyright: © Xue et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Lung cancer is the leading cause of cancer‑related mortality worldwide. Non‑small cell lung cancer (NSCLC) is the most common pathological subtype of lung cancer and is associated with low 5‑year overall survival rates. Therefore, novel and effective chemotherapeutic drugs are urgently required for improving the survival outcomes of patients with lung cancer. Cyclovirobuxine D (CVB‑D) is a natural steroidal alkaloid, used for the treatment of cardiovascular diseases in Traditional Chinese Medicine. Several studies have also demonstrated the antitumor effects of CVB‑D. Therefore, in the present study, the therapeutic effects of CVB‑D in lung cancer and the underlying mechanisms were investigated using the in vivo xenograft model of NSCLC in nude mice and in vitro experiments with the NSCLC cell lines. Bioinformatics analyses of RNA‑sequencing data, and cell‑based functional assays demonstrated that CVB‑D treatment significantly inhibited in vitro and in vivo NSCLC cell proliferation, survival, invasion, migration, angiogenesis, epithelial‑to‑mesenchymal transition and G₂/M phase cell cycle. CVB‑D exerted its antitumor effects by inhibiting the KIF11‑CDK1‑CDC25C‑cyclinB1 G₂/M phase transition regulatory oncogenic network and the NF‑κB/JNK signaling pathway. CVB‑D treatment significantly reduced the sizes and weights and malignancy of xenograft NSCLC tumors in the nude mice. In conclusion, the present study demonstrated that CVB‑D inhibited the growth and progression of NSCLC cells by inhibiting the KIF11‑CDK1‑CDC25C‑CyclinB1 G₂/M phase transition regulatory network and the NF‑κB/JNK signaling pathway. Therefore, CVB‑D is a promising drug for the treatment of NSCLC patients.

View Figures

View References

1	Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA and Jemal A: Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 68:394–424. 2018. View Article : Google Scholar : PubMed/NCBI
2	Inamura K: Lung Cancer: Understanding its molecular pathology and the 2015 WHO Classification. Front Oncol. 7:1932017. View Article : Google Scholar : PubMed/NCBI
3	Travis WD, Brambilla E, Burke AP, Marx A and Nicholson AG: Introduction to the 2015 World Health Organization Classification of tumors of the lung, pleura, thymus, and heart. J Thorac Oncol. 10:1240–1242. 2015. View Article : Google Scholar : PubMed/NCBI
4	Liu WJ, Du Y, Wen R, Yang M and Xu J: Drug resistance to targeted therapeutic strategies in Non-small cell lung cancer. Pharmacol Ther. 206:1074382020. View Article : Google Scholar
5	Garcia-Saez I and Skoufias DA: Eg5 targeting agents: From new anti-mitotic based inhibitor discovery to cancer therapy and resistance. Biochem Pharmacol. 184:1143642021. View Article : Google Scholar
6	Wei D, Rui B, Qingquan F, Chen C, Ping HY, Xiaoling S, Hao W and Jun G: KIF11 promotes cell proliferation via ERBB2/PI3K/AKT signaling pathway in gallbladder cancer. Int J Biol Sci. 17:514–526. 2021. View Article : Google Scholar : PubMed/NCBI
7	Neska-Dlugosz I, Buchholz K, Durslewicz J, Gagat M, Grzanka D, Tojek K and Klimaszewska-Wisniewska A: Prognostic impact and functional annotations of KIF11 and KIF14 expression in patients with colorectal cancer. Int J Mol Sci. 22:97322021. View Article : Google Scholar : PubMed/NCBI
8	Li TF, Zeng HJ, Shan Z, Ye RY, Cheang TY, Zhang YJ, Lu SH, Zhang Q, Shao N and Lin Y: Overexpression of kinesin super-family members as prognostic biomarkers of breast cancer. Cancer Cell Int. 20:1232020. View Article : Google Scholar
9	Schneider MA, Christopoulos P, Muley T, Warth A, Klingmueller U, Thomas M, Herth FJ, Dienemann H, Mueller NS, Theis F and Meister M: AURKA, DLGAP5, TPX2, KIF11 and CKAP5: Five specific mitosis-associated genes correlate with poor prognosis for non-small cell lung cancer patients. Int J Oncol. 50:365–372. 2017. View Article : Google Scholar : PubMed/NCBI
10	Fu F, Zhang Y, Gao Z, Zhao Y, Wen Z, Han H, Li Y and Chen H: Development and validation of a five-gene model to predict post-operative brain metastasis in operable lung adenocarcinoma. Int J Cancer. 147:584–592. 2020. View Article : Google Scholar : PubMed/NCBI
11	Li Z, Yu B, Qi F and Li F: KIF11 Serves as an independent prognostic factor and therapeutic target for patients with lung adenocarcinoma. Front Oncol. 11:6702182021. View Article : Google Scholar : PubMed/NCBI
12	Liu X, Liu X, Li J and Ren F: Identification and integrated analysis of key biomarkers for diagnosis and prognosis of non-small cell lung cancer. Med Sci Monit. 25:9280–9289. 2019. View Article : Google Scholar : PubMed/NCBI
13	Wang Z, Ma L, Su M, Zhou Y, Mao K, Li C, Peng G, Zhou C, Shen B and Dou J: Baicalin induces cellular senescence in human colon cancer cells via upregulation of DEPP and the activation of Ras/Raf/MEK/ERK signaling. Cell Death Dis. 9:2172018. View Article : Google Scholar : PubMed/NCBI
14	Pricci M, Girardi B, Giorgio F, Losurdo G, Ierardi E and Di Leo A: Curcumin and colorectal cancer: From basic to clinical evidences. Int J Mol Sci. 21:23642020. View Article : Google Scholar : PubMed/NCBI
15	Rauf A, Imran M, Butt MS, Nadeem M, Peters DG and Mubarak MS: Resveratrol as an anti-cancer agent: A review. Crit Rev Food Sci Nutr. 58:1428–1447. 2018. View Article : Google Scholar
16	Erin N, Grahovac J, Brozovic A and Efferth T: Tumor microenvironment and epithelial mesenchymal transition as targets to overcome tumor multidrug resistance. Drug Resist Updat. 53:1007152020. View Article : Google Scholar : PubMed/NCBI
17	Jiang Z, Fu L, Xu Y, Hu X, Yang H, Zhang Y, Luo H, Gan S, Tao L, Liang G and Shen X: Cyclovirobuxine D protects against diabetic cardiomyopathy by activating Nrf2-mediated antioxidant responses. Sci Rep. 10:64272020. View Article : Google Scholar : PubMed/NCBI
18	Zhou L, Tang H, Wang F, Ou S, Wu T, Fang Y, Xu J and Guo K: Cyclovirobuxine D inhibits cell proliferation and migration and induces apoptosis in human glioblastoma multiforme and lowgrade glioma. Oncol Rep. 43:807–816. 2020.PubMed/NCBI
19	Zhang J, Chen Y, Lin J, Jia R, An T, Dong T, Zhang Y and Yang X: Cyclovirobuxine D exerts anticancer effects by suppressing the EGFR-FAK-AKT/ERK1/2-slug signaling pathway in human hepatocellular carcinoma. DNA Cell Biol. 39:355–367. 2020. View Article : Google Scholar : PubMed/NCBI
20	Jiang F, Chen Y, Ren S, Li Z, Sun K, Xing Y, Zhu Y and Piao D: Cyclovirobuxine D inhibits colorectal cancer tumorigenesis via the CTHRC1AKT/ERKSnail signaling pathway. Int J Oncol. 57:183–196. 2020.PubMed/NCBI
21	Zeng C, Zou T, Qu J, Chen X, Zhang S and Lin Z: Cyclovirobuxine D Induced-mitophagy through the p65/BNIP3/LC3 axis potentiates its apoptosis-inducing effects in lung cancer cells. Int J Mol Sci. 22:58202021. View Article : Google Scholar : PubMed/NCBI
22	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar
23	Creamer-Hente MA, Lao FK, Dragos ZP and Waterman LL: Sex- and strain-related differences in the stress response of mice to CO₂ euthanasia. J Am Assoc Lab Anim Sci. 57:513–519. 2018. View Article : Google Scholar : PubMed/NCBI
24	Xie B, Wang S, Jiang N and Li JJ: Cyclin B1/CDK1-regulated mitochondrial bioenergetics in cell cycle progression and tumor resistance. Cancer Lett. 443:56–66. 2019. View Article : Google Scholar :
25	Cardano M, Tribioli C and Prosperi E: Targeting proliferating cell nuclear antigen (PCNA) as an effective strategy to inhibit tumor cell proliferation. Curr Cancer Drug Targets. 20:240–252. 2020. View Article : Google Scholar : PubMed/NCBI
26	Brabletz S, Schuhwerk H, Brabletz T and Stemmler MP: Dynamic EMT: A multi-tool for tumor progression. EMBO J. 40:e1086472021. View Article : Google Scholar : PubMed/NCBI
27	Chen Y, Liu P, Sun P, Jiang J, Zhu Y, Dong T, Cui Y, Tian Y, An T, Zhang J, et al: Oncogenic MSH6-CXCR4-TGFB1 feedback loop: A novel therapeutic target of photothermal therapy in glioblastoma multiforme. Theranostics. 9:1453–1473. 2019. View Article : Google Scholar : PubMed/NCBI
28	Pinzi L and Rastelli G: Molecular docking: Shifting paradigms in drug discovery. Int J Mol Sci. 20:43312019. View Article : Google Scholar : PubMed/NCBI
29	Socinski MA, Obasaju C, Gandara D, Hirsch FR, Bonomi P, Bunn P, Kim ES, Langer CJ, Natale RB, Novello S, et al: Clinicopathologic features of advanced squamous NSCLC. J Thorac Oncol. 11:1411–1422. 2016. View Article : Google Scholar : PubMed/NCBI
30	Duma N, Santana-Davila R and Molina JR: Non-small cell lung cancer: Epidemiology, screening, diagnosis, and treatment. Mayo Clin Proc. 94:1623–1640. 2019. View Article : Google Scholar : PubMed/NCBI
31	Herbst RS, Morgensztern D and Boshoff C: The biology and management of non-small cell lung cancer. Nature. 553:446–454. 2018. View Article : Google Scholar : PubMed/NCBI
32	Pastushenko I and Blanpain C: EMT Transition states during tumor progression and metastasis. Trends Cell Biol. 29:212–226. 2019. View Article : Google Scholar
33	Majidpoor J and Mortezaee K: Steps in metastasis: An updated review. Med Oncol. 38:32021. View Article : Google Scholar : PubMed/NCBI
34	Gavet O and Pines J: Progressive activation of CyclinB1-Cdk1 coordinates entry to mitosis. Dev Cell. 18:533–543. 2010. View Article : Google Scholar : PubMed/NCBI
35	Hong M, Tao S, Zhang L, Diao LT, Huang X, Huang S, Xie SJ, Xiao ZD and Zhang H: RNA sequencing: New technologies and applications in cancer research. J Hematol Oncol. 13:1662020. View Article : Google Scholar : PubMed/NCBI
36	Paczkowska M, Barenboim J, Sintupisut N, Fox NS, Zhu H, Abd-Rabbo D, Mee MW, Boutros PC, Drivers P; PCAWG Drivers and Functional Interpretation Working Group; et al: Integrative pathway enrichment analysis of multivariate omics data. Nat Commun. 11:7352020. View Article : Google Scholar : PubMed/NCBI
37	Venere M, Horbinski C, Crish JF, Jin X, Vasanji A, Major J, Burrows AC, Chang C, Prokop J, Wu Q, et al: The mitotic kinesin KIF11 is a driver of invasion, proliferation, and self-renewal in glioblastoma. Sci Transl Med. 7:304ra1432015. View Article : Google Scholar : PubMed/NCBI
38	Hu ZD, Jiang Y, Sun HM, Wang JW, Zhai LL, Yin ZQ and Yan J: KIF11 promotes proliferation of hepatocellular carcinoma among patients with liver cancers. Biomed Res Int. 2021:26767452021. View Article : Google Scholar : PubMed/NCBI
39	Liu J, Tian Y, Yi L, Gao Z, Lou M and Yuan K: High KIF11 expression is associated with poor outcome of NSCLC. Tumori. 108:40–46. 2022. View Article : Google Scholar
40	Yang Y, Zhang S and Guo L: Characterization of cell cycle-related competing endogenous RNAs using robust rank aggregation as prognostic biomarker in lung adenocarcinoma. Front Oncol. 12:8073672022. View Article : Google Scholar : PubMed/NCBI
41	Li S, Xuan Y, Gao B, Sun X, Miao S, Lu T, Wang Y and Jiao W: Identification of an eight-gene prognostic signature for lung adenocarcinoma. Cancer Manag Res. 10:3383–3392. 2018. View Article : Google Scholar : PubMed/NCBI
42	Wang L, Chen S, Luo Y, Yuan L, Peng T, Qian K, Liu X, Xiao Y and Wang X: Identification of several cell cycle relevant genes highly correlated with the progression and prognosis of human bladder urothelial tumor. J Cell Physiol. 234:13439–13451. 2019. View Article : Google Scholar : PubMed/NCBI
43	Meng F, Zhang L, Ren Y and Ma Q: Transcriptome analysis reveals key signature genes involved in the oncogenesis of lung cancer. Cancer Biomark. 29:475–482. 2020. View Article : Google Scholar : PubMed/NCBI
44	Gong K, Zhou H, Liu H, Xie T, Luo Y, Guo H, Chen J, Tan Z, Yang Y and Xie L: Identification and integrate analysis of key biomarkers for diagnosis and prognosis of non-small cell lung cancer based on bioinformatics analysis. Technol Cancer Res Treat. 20:153303382110602022021. View Article : Google Scholar : PubMed/NCBI
45	Gao L, Xia S, Zhang K, Lin C, He X and Zhang Y: Gene expression profile of THZ1-treated nasopharyngeal carcinoma cell lines indicates its involvement in the inhibition of the cell cycle. Transl Cancer Res. 10:445–460. 2021. View Article : Google Scholar
46	Guido BC, Ramos LM, Nolasco DO, Nobrega CC, Andrade BY, Pic-Taylor A, Neto BA and Correa JR: Impact of kinesin Eg5 inhibition by 3,4-dihydropyrimidin-2(1H)-one derivatives on various breast cancer cell features. BMC Cancer. 15:2832015. View Article : Google Scholar : PubMed/NCBI
47	Jiang M, Zhuang H, Xia R, Gan L, Wu Y, Ma J, Sun Y and Zhuang Z: KIF11 is required for proliferation and self-renewal of docetaxel resistant triple negative breast cancer cells. Oncotarget. 8:92106–92118. 2017. View Article : Google Scholar : PubMed/NCBI
48	Thankamony AP, Murali R, Karthikeyan N, Varghese BA, Teo WS, McFarland A, Roden DL, Holliday H, Konrad CV, Cazet A, et al: Targeting the Id1-Kif11 Axis in triple-negative breast cancer using combination therapy. Biomolecules. 10:12952020. View Article : Google Scholar : PubMed/NCBI
49	Kato T, Lee D, Wu L, Patel P, Young AJ, Wada H, Hu HP, Ujiie H, Kaji M, Kano S, et al: Kinesin family members KIF11 and KIF23 as potential therapeutic targets in malignant pleural mesothelioma. Int J Oncol. 49:448–456. 2016. View Article : Google Scholar : PubMed/NCBI
50	Zhou Y, Yang L, Xiong L, Wang K, Hou X, Li Q, Kong F, Liu X and He J: KIF11 is upregulated in colorectal cancer and silencing of it impairs tumor growth and sensitizes colorectal cancer cells to oxaliplatin via p53/GSK3beta signaling. J Cancer. 12:3741–3753. 2021. View Article : Google Scholar :
51	Liu K, Zheng M, Lu R, Du J, Zhao Q, Li Z, Li Y and Zhang S: The role of CDC25C in cell cycle regulation and clinical cancer therapy: A systematic review. Cancer Cell Int. 20:2132020. View Article : Google Scholar : PubMed/NCBI
52	Takizawa CG and Morgan DO: Control of mitosis by changes in the subcellular location of cyclin-B1-Cdk1 and Cdc25C. Curr Opin Cell Biol. 12:658–665. 2000. View Article : Google Scholar : PubMed/NCBI
53	Wang JN, Zhang ZR, Che Y, Yuan ZY, Lu ZL, Li Y, Li N, Wan J, Sun HD, Sun N, et al: Acetyl-macrocalin B, an ent-kaurane diterpenoid, initiates apoptosis through the ROS-p38-caspase 9-dependent pathway and induces G2/M phase arrest via the Chk1/2-Cdc25C-Cdc2/cyclin B axis in non-small cell lung cancer. Cancer Biol Ther. 19:609–621. 2018. View Article : Google Scholar : PubMed/NCBI
54	Wu Q, Wu W, Jacevic V, Franca TCC, Wang X and Kuca K: Selective inhibitors for JNK signalling: A potential targeted therapy in cancer. J Enzyme Inhib Med Chem. 35:574–583. 2020. View Article : Google Scholar : PubMed/NCBI
55	Bubici C and Papa S: JNK signalling in cancer: In need of new, smarter therapeutic targets. Br J Pharmacol. 171:24–37. 2014. View Article : Google Scholar :
56	Abdelrahman KS, Hassan HA, Abdel-Aziz SA, Marzouk AA, Narumi A, Konno H and Abdel-Aziz M: JNK signaling as a target for anticancer therapy. Pharmacol Rep. 73:405–434. 2021. View Article : Google Scholar : PubMed/NCBI
57	Song W, Ma Y, Wang J, Brantley-Sieders D and Chen J: JNK signaling mediates EPHA2-dependent tumor cell proliferation, motility, and cancer stem cell-like properties in non-small cell lung cancer. Cancer Res. 74:2444–2454. 2014. View Article : Google Scholar : PubMed/NCBI
58	Dou Y, Jiang X, Xie H, He J and Xiao S: The Jun N-terminal kinases signaling pathway plays a 'seesaw' role in ovarian carcinoma: A molecular aspect. J Ovarian Res. 12:992019. View Article : Google Scholar
59	Wang J and Tai G: Role of C-Jun N-terminal kinase in hepatocellular carcinoma development. Target Oncol. 11:723–738. 2016. View Article : Google Scholar : PubMed/NCBI
60	Gutierrez GJ, Tsuji T, Cross JV, Davis RJ, Templeton DJ, Jiang W and Ronai ZA: JNK-mediated phosphorylation of Cdc25C regulates cell cycle entry and G(2)/M DNA damage checkpoint. J Biol Chem. 285:14217–14228. 2010. View Article : Google Scholar : PubMed/NCBI
61	Udden SN, Kwak YT, Godfrey V, Khan MAW, Khan S, Loof N, Peng L, Zhu H and Zaki H: NLRP12 suppresses hepatocellular carcinoma via downregulation of cJun N-terminal kinase activation in the hepatocyte. Elife. 8:e403962019. View Article : Google Scholar : PubMed/NCBI
62	Han YH, Mun JG, Jeon HD, Park J, Kee JY and Hong SH: Gomisin A ameliorates metastatic melanoma by inhibiting AMPK and ERK/JNK-mediated cell survival and metastatic phenotypes. Phytomedicine. 68:1531472020. View Article : Google Scholar : PubMed/NCBI
63	Okada M, Shibuya K, Sato A, Seino S, Watanabe E, Suzuki S, Seino M and Kitanaka C: Specific role of JNK in the maintenance of the tumor-initiating capacity of A549 human non-small cell lung cancer cells. Oncol Rep. 30:1957–1964. 2013. View Article : Google Scholar : PubMed/NCBI
64	Cheng J, Li M, Tzeng CM, Gou X and Chen S: Suppression of tumorigenicity 5 ameliorates tumor characteristics of invasive breast cancer cells via ERK/JNK Pathway. Front Oncol. 11:6215002021. View Article : Google Scholar : PubMed/NCBI
65	Baud V and Karin M: Is NF-kappaB a good target for cancer therapy? Hopes and pitfalls. Nat Rev Drug Discov. 8:33–40. 2009. View Article : Google Scholar : PubMed/NCBI
66	Hoesel B and Schmid JA: The complexity of NF-κB signaling in inflammation and cancer. Mol Cancer. 12:862013. View Article : Google Scholar
67	Rasmi RR, Sakthivel KM and Guruvayoorappan C: NF-κB inhibitors in treatment and prevention of lung cancer. Biomed Pharmacother. 130:1105692020. View Article : Google Scholar
68	Sarkar FH and Li Y: NF-kappaB: A potential target for cancer chemoprevention and therapy. Front Biosci. 13:2950–2959. 2008. View Article : Google Scholar
69	Fouani L, Kovacevic Z and Richardson DR: Targeting oncogenic nuclear factor Kappa B Signaling with redox-active agents for cancer treatment. Antioxid Redox Signal. 30:1096–1123. 2019. View Article : Google Scholar
70	Suhail M, Tarique M, Muhammad N, Naz H, Hafeez A, Zughaibi TA, Kamal MA and Rehan M: A critical transcription factor NF-κB as a cancer therapeutic target and its inhibitors as cancer treatment options. Curr Med Chem. 28:4117–4132. 2021. View Article : Google Scholar
71	Khan H, Ullah H, Castilho P, Gomila AS, D'Onofrio G, Filosa R, Wang F, Nabavi SM, Daglia M, Silva AS, et al: Targeting NF-κB signaling pathway in cancer by dietary polyphenols. Crit Rev Food Sci Nutr. 60:2790–2800. 2020. View Article : Google Scholar
72	Rajagopal C, Lankadasari MB, Aranjani JM and Harikumar KB: Targeting oncogenic transcription factors by polyphenols: A novel approach for cancer therapy. Pharmacol Res. 130:273–291. 2018. View Article : Google Scholar : PubMed/NCBI
73	Ashrafizadeh M, Najafi M, Makvandi P, Zarrabi A, Farkhondeh T and Samarghandian S: Versatile role of curcumin and its derivatives in lung cancer therapy. J Cell Physiol. 235:9241–9268. 2020. View Article : Google Scholar : PubMed/NCBI
74	Saijo T, Ishii G, Ochiai A, Yoh K, Goto K, Nagai K, Kato H, Nishiwaki Y and Saijo N: Eg5 expression is closely correlated with the response of advanced non-small cell lung cancer to antimitotic agents combined with platinum chemotherapy. Lung Cancer. 54:217–225. 2006. View Article : Google Scholar : PubMed/NCBI
75	Lv P, Man S, Xie L, Ma L and Gao W: Pathogenesis and therapeutic strategy in platinum resistance lung cancer. Biochim Biophys Acta Rev Cancer. 1876:1885772021. View Article : Google Scholar : PubMed/NCBI
76	Wang LH, Li Y, Yang SN, Wang FY, Hou Y, Cui W, Chen K, Cao Q, Wang S, Zhang TY, et al: Gambogic acid synergistically potentiates cisplatin-induced apoptosis in non-small-cell lung cancer through suppressing NF-κB and MAPK/HO-1 signalling. Br J Cancer. 110:341–352. 2014. View Article : Google Scholar
77	Wang J, Tian L, Khan MN, Zhang L, Chen Q, Zhao Y, Yan Q, Fu L and Liu J: Ginsenoside Rg3 sensitizes hypoxic lung cancer cells to cisplatin via blocking of NF-κB mediated epithelial-mesenchymal transition and stemness. Cancer Lett. 415:73–85. 2018. View Article : Google Scholar
78	Cui H, Arnst K, Miller DD and Li W: Recent advances in elucidating paclitaxel resistance mechanisms in non-small cell lung cancer and strategies to overcome drug resistance. Curr Med Chem. 27:6573–6595. 2020. View Article : Google Scholar : PubMed/NCBI
79	Jiang N, Dong XP, Zhang SL, You QY, Jiang XT and Zhao XG: Triptolide reverses the Taxol resistance of lung adenocarcinoma by inhibiting the NF-κB signaling pathway and the expression of NF-κB-regulated drug-resistant genes. Mol Med Rep. 13:153–159. 2016. View Article : Google Scholar
80	Li DD, Qin XC, Yang Y, Chu HX, Li RL, Ma LX, Ding HW and Zhao QC: Daurinoline suppressed the migration and invasion of chemo-resistant human non-small cell lung cancer cells by reversing EMT and Notch-1 and sensitized the cells to Taxol. Environ Toxicol Pharmacol. 66:109–115. 2019. View Article : Google Scholar : PubMed/NCBI
81	Li Y and Zhang H: Nanoparticle-based drug delivery systems for enhanced tumor-targeting treatment. J Biomed Nanotechnol. 15:1–27. 2019. View Article : Google Scholar