异丙酚对卵巢癌进展和顺铂敏感性的影响及机制

Effects of propofol on progression of ovarian cancer cells and cis-platinum sensitivity and its mechanism

目的探讨异丙酚对卵巢癌进展及顺铂(DDP)敏感性的影响及机制。方法取对数生长期的卵巢癌细胞A2780和耐DDP卵巢癌细胞A2780/DDP,分别与异丙酚(0、1、5、10及20 mg/L)和DDP(0、5、10、20、40及80μmol/L)进行孵育,采用CCK-8法观察A2780和A2780/DDP细胞存活率;取对数生长期的A2780和A2780/DDP细胞分为Control组(等量培养基)、异丙酚组(10 mg/L异丙酚)、DDP组(10μmol/L DDP)、异丙酚+DDP组(10 mg/L异丙酚+10μmol/L DDP),克隆形成实验观察细胞克隆数,流式细胞仪检测细胞凋亡,Western blot检测凋亡蛋白B细胞淋巴瘤-XL(Bcl-xl)单克隆抗体、细胞凋亡调节因子(Bim)及活化半胱氨酸蛋白酶-3(cleaved caspase-3)表达,Transwell检测各组A2780和A2780/DDP细胞的侵袭;裸鼠移植瘤实验观察各组肿瘤生长情况。结果A2780、A2780/DDP细胞活力随异丙酚和DDP浓度升高均下降,A2780/DDP细胞系半抑制浓度(IC50)均高于A2780细胞系(P<0.05);与Control组相比,异丙酚组和DDP组A2780、A2780/DDP细胞系细胞活力、细胞克隆数、细胞侵袭率及Bcl-xl表达均下降,细胞凋亡率、Bim和cleaved caspase-3表达均上升(P<0.05);与DDP组相比,异丙酚+DDP组A2780、A2780/DDP细胞系细胞活力、细胞克隆数、细胞侵袭率及Bcl-xl表达均下降,细胞凋亡率、Bim及cleaved caspase-3表达均上升(P<0.05);异丙酚组和DDP组裸鼠肿瘤质量和肿瘤体积均较Control组和DDP组下降(P<0.05)。结论异丙酚可增强DDP对卵巢癌细胞生长的抑制作用,其机制可能与增加DDP细胞毒性、细胞凋亡、DDP敏感性及抑制肿瘤细胞侵袭行为有关。

Objective To explore the effects of propofol on the progression of ovarian cancer cells and cis-platinum(DDP)sensitivity.Methods A2780 and A2780/DDP cells in logarithmic phase were incubated with propofol(0,1,5,10,and 20 mg/L)and DDP(0,5,10,20,40,and 80μmol/L),respectively.The survival rates of A2780 and A2780/DDP cells were detected by cell counting kit(CCK-8).The above cells were divided into Control group(equal medium),Propofol group(10 mg/L propofol),DDP group(10μmol/L DDP)and Propofol+DDP group(10 mg/L propofol+10μmol/L DDP).The clone number of A2780 and A2780/DDP cells was detected by clone formation assay.The apoptosis of A2780 and A2780/DDP cells was detected by flow cytometry.The expressions of apoptosis proteins[rat B-cell lymphoma-XL(Bcl-xl)monoclonal antibody,bcl-2 interacting mediator of cell death(Bim),cleaved cysteine proteinase-3(cleaved caspase-3)]were detected by Western blot.The invasion of A2780 and A2780/DDP cells was detected by Transwell.The growth of tumors was observed by transplanted tumor assay in nude mice.Results With the increase of Propofol and DDP concentrations,the activities of A2780 and A2780/DDP cells decreased significantly.50%inhibiting concertration(IC 50)of A2780/DDP cell lines was significantly higher than that of A2780 cell line(P<0.05).Compared with Control group,the activities of A2780 and A2780/DDP cell lines,number of clone cells,invasion rate of cells and Bcl-xl decreased significantly in Propofol group and DDP group,while apoptosis rate,expressions of Bim and cleaved caspase-3 increased significantly(P<0.05).Compared with DDP group,the activities of A2780 and A2780/DDP cell lines,number of clone cells,invasion rate of cells and Bcl-xl decreased significantly in Propofol+DDP group,while apoptosis rate,expressions of Bim and cleaved caspase-3 increased significantly(P<0.05).Compared with Control group,the mass and volume of tumors decreased significantly in Propofol group,DDP group and Propofol+DDP group(P<0.05).Compared with DDP group,the mass and volume of tumors decreased significantly in Propofol+DDP group(P<0.05).Conclusion Propofol can increase cell apoptosis and DDP sensitivity,and inhibit tumor cell invasion by enhancing cytotoxicity of DDP cells,thus enhancing inhibiting effect of DDP on tumor growth.