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作 者:刘健培[1] 黄品婕[2] 郑宗珩[1] 张实[1] 卫洪波[1]
机构地区:[1]中山大学附属第三医院胃肠外科,广东广州510630 [2]中山大学附属第三医院麻醉科,广东广州510630
出 处:《中国医院药学杂志》2015年第5期396-400,共5页Chinese Journal of Hospital Pharmacy
基 金:广东省自然博士启动科学基金资助(编号:S2012040006569)
摘 要:目的:探讨塞来昔布联合全反式维甲酸抑制结肠癌SW620细胞增殖和促进凋亡的作用及机制。方法:不同浓度塞来昔布和全反式维甲酸作用SW620细胞48或72 h后应用MTT法和流式细胞仪分别检测细胞的增殖抑制和凋亡率,Western Blot检测细胞AKT、p-AKT及survivin的表达。结果:与单药作用相比,塞来昔布和全反式维甲酸联合作用可明显增强对SW620的增殖抑制和促进凋亡作用(P均<0.01)。Western Blot提示全反式维甲酸和塞来昔布联合作用SW620细胞可抑制AKT活性,下调p-AKT和survivin蛋白表达。结论:塞来昔布在抑制结直肠癌细胞增殖和促进其凋亡中与全反式维甲酸起协同作用,抑制AKT磷酸化、阻断PI3K/Akt通路和下调survivin是其可能作用机制。此结果有望为临床提供可行的联合用药方案,推广维甲酸的诱导分化和凋亡治疗。OBJECTIVE To investigate the effects and underlying mechanisms of all trans retinoic acid (ATRA) combined with eelecoxib on proliferation and apoptosis of human colon cancer SW620 cell lines. METHODS The human colon cancer SW620 cell lines were treated by ATRA and celecoxib alone or in combination. Proliferation was detected by MTT method, apoptosis by flow cytometry, expressions of serine threonine kinase (AKT), phosphorylated AKT and survivin were measured by western blot. RESULTS ATRA or celecoxib at clinical concentrations alone had no effect on SW620 cell lines, but when combined with celecoxib, ATRIA inhibited proliferation and induced apoptosis in dose dependent and time dependent manners. In accordance with the enhanced anticancer effects of celecoxib and ATRA combination, expressions of phosphorylated AKT and survivin protein markedly decreased in SW620 cell lines. CONCLUSION Celecoxib and ATRA showed synergistic effects of proliferation inhibiting and apoptosis inducing on human colon cancer SW620 cell lines through increasing expressions of phos-phorylated AKT and survivin protein.
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