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作 者:Liu Minghua Yang Ying Liu Dajun Cao Ye Li Yan
机构地区:[1]Department of Gastroenterology,China Medical University Affiliated Shengjing Hospital,Shenyang 110002,China [2]Department of Renal Medicine,China Medical University Affiliated Shengjing Hospital,Shenyang 110002,China
出 处:《Journal of Traditional Chinese Medicine》2020年第6期908-916,共9页中医杂志(英文版)
基 金:Supported by the Science and Technology Program of Liaoning Province(No.2009225034);Research of Parthenolide Inhibit Gastric Cancer and Increase Chemotherapy Sensitivity。
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,SGC7901/DDP,and SGC7901/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-κB),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-κB 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-κB,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.
关 键 词:PARTHENOLIDE CISPLATIN ADRIAMYCIN Gastric cancer CHEMOTHERAPY Sensitivity
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