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OACSTPCD
Propofol Improved the Proliferation,G2/M Phase Arrest and Radiation Resistance of Cervical Cancer Cells Induced by Cobalt Chloride
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:CoCl2 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:CoCl2 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,CoCl2 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CoCl2 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CoCl2 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(CoCl2)in on cervical cancer Hela cells and its relationship with HIF-1α and VEGF.Methods:CoCl2 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-1α and VEGF were detected by crystal violet staining,flow cytometry,cloning formation experiments,real-time quantitative PCR,western blotting and enzyme-linked immunosorbent assays,respectively.Results:Propofol inhibited the proliferation of Hela cells induced by CoCl2 in a dose-dependent manner.Compared with the control group,CoCl2 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 CoCl2-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-1 α and VEGF induced by CoCl2 treatment(P<0.001).Conclusion:Propofol might reverse anoxia-induced proliferation,G2/M phase arrest and radiation resistance by downregulating the expression of HIF-1α and VEGF in Hela cells.
毛远舟;郭巧姗;黄建鸣;邹江;陈一丁;张可贤;舒进军
610041 成都,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||610041 成都,四川省骨科医院麻醉科610041 成都,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610041 成都,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
临床医学
宫颈癌丙泊酚氯化钴辐射抗性HIF-1 αVEGF
Cervical cancerPropofolCobalt chlorideRadiation resistanceHIF-1 αVEGF
《肿瘤预防与治疗》 2024 (002)
101-109 / 9
This study was supported by grants from Science and Technology Department of Sichuan Province(No.2020YFS0419),Sichuan Medical Association(No.S19019)and Sichuan Cancer Hospital(No.YB2016006). 四川省科技厅重点研发项目(编号:2020 YFS0419);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)
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