Parthenolide increases the sensitivity of gastric cancer cells to chemotherapy

• 作者: Liu Minghua Yang Ying Liu Dajun Cao Ye Li Yan
• 来源期刊: 中医杂志（英文版）
• 年，卷（期）: 2020,（6）
• 所属期刊栏目: Research Articles
• 页码范围: 908-916
• 页数: 9页
• 语种: 英文

摘要

OBJECTIVE: To investigate the effect of parthenolide (PTL),a sesquiterpene lactone medicinal compound,on the sensitivity of the gastric cancer cell line SGC7901 and the DPP-and ADR-resistant sublines SGC7901/DDP and SGC7901/ADR to cisplatin[diamminedichloroplatinum (Ⅱ),DDP]and adriamycin (ADR) in vitro.METHODS: SGC7901,SGC790 1/DDP,a nd SGC790 1/ADR were treated with various concentrations of PTL alone or in combination with DDP or ADR.The effects on cell proliferation,apoptosis,and expression/activity of several proliferation/apoptosis-related proteins[B-cell lymphoma-2 (Bcl-2),cyclin D1,nuclear factor-kappa B (NF-KB),and Caspase-8]and drug transporters (P-glycoprotein and multidrug resistance protein-1) were measured using flow cytometry,Western blotting,and in vitro activity assays.RESULTS: Treatment of SGC7901 cells with PTL inhibited cell growth,increased apoptosis,and sensitized the cells to DPP.Mechanistically,PTL treatment resulted in downregulation of NF-KB activity and Bcl-2 expression,and upregulation of Caspase-8 activity.Similarly,PTL co-treatment of SGC7901/DDP and SGC7901/ADR overcame their resistance to DDP and ADR,respectively,with concomitant inhibition of NF-KB,Bcl-2,Cyclin D1,P-glycoprotein,and multidrug resistance protein-1 expression and/or activity.CONCLUSION: PTL treatment decreases drug resistance in SGC7901,SGC7901/DDP,and SGC7901/ADR cells,as reflected by induction of apoptosis,inhibition of proliferation,downregulation of pro-survival and drug resistance pathways,and upregulation of pro-apoptotic pathways.Our results suggest that co-treatment with PTL may thus complement existing therapies for gastric cancer.