丙泊酚改善缺氧诱导的宫颈癌细胞增殖、G2/M期阻滞和辐射抗性  

Propofol Improved the Proliferation,G2/M Phase Arrest and Radiation Resistance of Cervical Cancer Cells Induced by Cobalt Chloride

作　　者：毛远舟[1,3] 郭巧姗 黄建鸣 邹江[1] 陈一丁[1] 张可贤[1] 舒进军[1] Mao Yuanzhou;Guo Qiaoshan;Huang Jianming;Zou Jiang;Chen Yiding;Zhang Kexian;Shu Jinjun(Department of Anesthesia,Sichuan Clinical Research Center for Cancer,Sichuan Cancer Hospital&Institute,Sichuan Cancer Center,Affiliated Cancer Hospital of University of Electronic Science and Technology of China,Chengdu 610041,Sichuan,China;Research Institute,Sichuan Clinical Research Center for Cancer,Sichuan Cancer Hospital&Institute,Sichuan Cancer Center,Affiliated Cancer Hospital of University of Electronic Science and Technology of China,Chengdu 610041,Sichuan,China;Department of Anesthesiology,Sichuan Orthopedic Hospital,Chengdu 610041,Sichuan,China)

机构地区：[1]四川省肿瘤临床医学研究中心,四川省肿瘤医院·研究所,四川省癌症防治中心,电子科技大学附属肿瘤医院麻醉科,成都610041 [2]四川省肿瘤临床医学研究中心,四川省肿瘤医院·研究所,四川省癌症防治中心,电子科技大学附属肿瘤医院实验研究部,成都610041 [3]四川省骨科医院麻醉科,成都610041

出　　处：《肿瘤预防与治疗》2024年第2期101-109,共9页Journal of Cancer Control And Treatment

基　　金：四川省科技厅重点研发项目(编号:2020YFS0419);四川省医学会科研课题(编号:S19019);四川省肿瘤医院麻醉学重点学科基金(编号:YB2016006)。

摘　　要：目的:探讨丙泊酚对氯化钴环境下宫颈癌Hela细胞的增殖、G2/M期阻滞和抗辐射抵抗作用及其与HIF-1α和VEGF的关系。方法:CoCl_(2)诱导Hela细胞构建缺氧化学模型;结晶紫染色检测细胞增殖活性;流式细胞术检测细胞周期;克隆形成实验检测细胞辐射敏感性;荧光定量PCR检测HIF-1α和VEGF转录水平表达;免疫印迹和酶联免疫吸附实验检测HIF-1α和VEGF蛋白水平表达。结果:CoCl_(2)处理条件下丙泊酚抑制Hela细胞增殖,且呈剂量依赖性;与对照组相比,CoCl_(2)处理诱导了G0/G1/S期细胞比例显著增加和G2/M期细胞比例显著减少(P<0.001),而丙泊酚处理后显著反转了此结果(P<0.001);在CoCl_(2)处理后的Hela细胞中,丙泊酚降低0、1、2、4 Gy剂量辐射后Dq、SF2和D0值;机制上,丙泊酚处理恢复了CoCl_(2)处理诱导的HIF-1α和VEGF转录和翻译表达水平的下调(P<0.001)。结论:丙泊酚可通过下调宫颈癌Hela细胞HIF-1α和VEGF的表达来逆转缺氧诱导的增殖、G2/M期阻滞和辐射抵抗。Objective:To investigate the effect of propofol on the proliferation,G2/M phase arrest and radiation resistance induced cobalt chloride(CoCl_(2))in on cervical cancer Hela cells and its relationship with HIF-1αand VEGF.Methods:CoCl_(2) was employed to construct a hypoxia model in Hela cells.The cell proliferative activity,cell cycle,cell radiation sensitivity,the relative mRNA and protein expression levels of HIF-1αand VEGF were detected by crystal violet staining,flow cytometry,cloning formation experiments,real-time quantitative PCR,western blotting and enzymelinked immunosorbent assays,respectively.Results:Propofol inhibited the proliferation of Hela cells induced by CoCl_(2) in a dose-dependent manner.Compared with the control group,CoCl_(2) treatment induced a significant increase in the proportion of cells in the G0/G1/S phase and a significant decrease in the proportion of cells in the G2/M phase(P<0.001),which were significantly reversed after propofol treatment(P<0.001).In CoCl_(2)-treated Hela cells,propofol reduced Dq,SF2,and D0 values after radiation at 0,1,2,and 4 Gy dose,and restored the down-regulation of transcriptional and translational expression levels of HIF-1αand VEGF induced by CoCl_(2) treatment(P<0.001).Conclusion:Propofol might reverse anoxia-induced proliferation,G2/M phase arrest and radiation resistance by downregulating the expression of HIF-1αand VEGF in Hela cells.

关 键 词：宫颈癌 丙泊酚 氯化钴 辐射抗性 HIF-1α VEGF 

分 类 号：R737.33[医药卫生—肿瘤] R730.231[医药卫生—临床医学]