Study on the cisplatin-sensitization effect of tripterygium glycosides on cisplatin-resistant human epithelial ovarian cancer cells (SKOV3/DDP) in vitro

Abstract

Abstract:

AIM: To study the cisplatin-sensitization effect and mechanism of tripterygium glycosides on cisplatin-resistant human epithelial ovarian cancer cells (SKOV3/DDP). METHODS: The SKOV3/DDP cells in exponential phase of growth were randomly divided into eight groups:blank control group, 10 μg/mL DDP group, 50 μg/mL GTW group, 800 μg/mL GTW group, 3 200 μg/mL GTW group, 10 μg/mL DDP+50 μg/mL GTW group, 10 μg/mL DDP+800 μg/mL GTW group and 10 μg/mL DDP+3 200 μg/mL GTW group. Cell counting kit 8 and flow cytometry and western blot were used to detect the growth inhibiting rate and apoptosis rate and relative expression of GST-π, MDR1, STAT3, p-STAT3 of SKOV3/DDP cells of every group. RESULTS:DDP and GTW produce an additive effect when used concurrently in inhibiting growth of SKOV3/DDP cells. 800 μg/mL GTW or 3 200 μg/mL GTW combined with 10 μg/mL DDP can significantly induce apoptosis of SKOV3/DDP cells and down-regulate the expression of p-STAT3 (P<0.05). CONCLUSION: GTW can significantly enhance sensitivity of SKOV3/DDP cells to DDP. The underlying mechanism may be related with down-regulating the expression of p-STAT3 in STAT3 pathway.

Key words: tripterygium glycosides, SKOV3/DDP, cisplatin, cisplatin-sensitization effect, STAT3

CLC Number:

LIU Wencheng，TAN Buzhen，ZHAN Xinlu，HU Hui，HUANG Genhua，CAO Qing. Study on the cisplatin-sensitization effect of tripterygium glycosides on cisplatin-resistant human epithelial ovarian cancer cells (SKOV3/DDP) in vitro[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2017, 22(12): 1364-1370.

References

［1］Li CX, Li TS, Zhu Z, et al. Advance in studies on anti-inflammatory and immunoregulatory monomers of Tripterygium wilfordii［J］. Zhongguo Zhong Yao Za Zhi, 2014, 39(21): 4159- 4164.
［2］Wang Q, Meng J, Dong A, et al. The pharmacological effects and mechanism of tripterygium wilfordii hook F in central nervous system autoimmunity ［J］. J Altern Complement Med, 2016, 22(7): 496-502.
［3］Ma ZJ, Zhang XN, Li L, et al. Tripterygium glycosides tablet ameliorates renal tubulointerstitial fibrosis via the toll-like receptor 4/nuclear factor kappa B signaling pathway in high-fat diet fed and streptozotocin-induced diabetic rats ［J］. J Diabetes Res, 2015: 390428.
［4］Huang ZJ, Que HQ, Peng HY, et al. Reproductive toxicity of triptolide and its mechanism in male rats ［J］. Zhongguo Zhong Yao Za Zhi, 2015, 40(23): 4655-4659.
［5］Huang J, Zhang JQ, Chen Z, et al. Systematic evaluation for efficacy of tripterygium glycosides in treating diabetic nephropathy stage IV［J］. Zhongguo Zhong Yao Za Zhi, 2015, 40(15): 3100-3109.
［6］Wang HL, Jiang Q, Feng XH, et al. Tripterygium wilfordii Hook F versus conventional synthetic disease-modifying anti-rheumatic drugs as monotherapy for rheumatoid arthritis: a systematic review and network meta-analysis［J］. BMC Complement Altern Med, 2016, 16: 215.
［7］Tallarida RJ. Drug synergism: its detection and applications ［J］. JPET,2001, 298: 865-872.
［8］Elvira C, Linda V, Mariangela I, et al. Photodynamic therapy with indocyanine green complements and enhances low-dose cisplatin cytotoxicity in MCF-7 breast cancer cells ［J］. Mol Cancer Ther, 2004, 3: 537-544.
［9］Dimitri P, Nicolas D, Muriel G, et al. Chemosensitizing effects of sphingosine kinase-1 inhibition in prostate cancer cell and animal models ［J］. Mol Cancer Ther, 2008, 7(7): 1836-1845.
［10］Gao Y, Rankin GO, Tu Y, et al. Theaflavin-3, 3'-digallate decreases human ovarian carcinoma OVCAR-3 cell-induced angiogenesis via Akt and Notch-1 pathways, not via MAPK pathways ［J］. Int J Oncol, 2016, 48(1): 281-292.
［11］Shin K, Kim KH, Yoon MS, et al. Expression of interactive genes associated with apoptosis and their prognostic value for ovarian serous adenocarcinoma ［J］. Adv Clin Exp Med, 2016, 25(3): 513-521.
［12］Sung PL, Jan YH, Lin SC, et al. Periostin in tumor microenvironment is associated with poor prognosis and platinum resistance in epithelial ovarian carcinoma［J］. Oncotarget, 2016, 7(4): 4036-4047.
［13］Zhang M, Luo SC. Gene expression profiling of epithelial ovarian cancer reveals key genes and pathways associated with chemotherapy resistance［J］. Genet Mol Res, 2016, 15(1): gmr.15017496.
［14］Zhang J, Grek C, Ye ZW, et al. Pleiotropic functions of glutathione S-transferase P［J］. Adv Cancer Res, 2014, 122: 143-175.
［15］张珂, 杨兴升, 孙彩萍, 等. 谷胱甘肽转移酶π基因在COC1/DDP细胞对顺铂耐药的作用［J］. 中华外科学杂志, 2015, 32(4): 874-876.
［16］Jun Y, Peng Z, James A, et al. Advances in plant-based inhibitors of P-glycoprotein［J］. J Enzyme Inhib Med Chem, 2016, 31(6): 867-881.
［17］Chen S, Jiao JW, Sun KX, et al. MicroRNA-133b targets glutathione S-transferase π expression to increase ovarian cancer cell sensitivity to chemotherapy drugs［J］. Drug Des Devel Ther, 2015, 9: 5225-5235.
［18］Siveen KS, Sikka S, Surana R, et al. Targeting the STAT3 signaling pathway in cancer: role of synthetic and natural inhibitors［J］. Biochim Biophys Acta, 2014, 1845(2): 136-154.
［19］Huang W, Dong Z, Chen Y, et al. Small-molecule inhibitors targeting the DNA-binding domain of STAT3 suppress tumor growth, metastasis and STAT3 target gene expression in vivo ［J］. Oncogene, 2016, 35(6): 783-792.
［20］Liu S, Sun J, Cai B, et al. NANOG regulates epithelial-mesenchymal transition and chemoresistance through activation of the STAT3 pathway in epithelial ovarian cancer ［J］. Tumor Biol, 2016, 37(7): 9671-9680.
［21］Park J, Park SY, Kim JH. Leukotriene B4 receptor-2 contributes to chemoresistance of SKOV-3 ovarian cancer cells through activation of signal transducer and activator of transcription-3-linked cascade ［J］. Biochim Biophys Acta, 2016, 1863(2): 236-243.
［22］Permuth-Wey J, Fulp WJ, Reid BM, et al. STAT3 polymorphisms may predict an unfavorable response to first-line platinum-based therapy for women with advanced serous epithelial ovarian cancer ［J］. Int J Cancer, 2016, 138(3): 612-619.
［23］Tang YJ, Sun ZL, Wu WG, et al. Inhibitor of signal transducer and activator of transcription 3 (STAT3) suppresses ovarian cancer growth, migration and invasion and enhances the effect of cisplatin in vitro［J］. Genet Mol Res, 2015, 14(1): 2450-2460.
［24］Gritsina G, Xiao F, O'Brien SW, et al. Targeted blockade of JAK/STAT3 signaling inhibits ovarian carcinoma growth［J］. Mol Cancer Ther, 2015, 14(4): 1035-1047.
［25］Yang Z, Liu Y, Liao J, et al. Quercetin induces endoplasmic reticulum stress to enhance cDDP cytotoxicity in ovarian cancer: involvement of STAT3 signaling ［J］. FEBS J, 2015, 282(6): 1111-1125.

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