乏氧条件下坎地沙坦增加肺腺癌A549细胞放射敏感性

Candesartan increases radiosensitivity of lung adenocarcinoma A549 cells in hypoxic condition

目的:探讨乏氧条件下坎地沙坦对肺腺癌A549细胞放射敏感性的影响及其机制。方法:将A549细胞分为常氧组、乏氧组和坎地沙坦+乏氧组,ELISA检测血管紧张素Ⅱ(AngⅡ)的表达,Western blot检测乏氧诱导因子1α(HIF-1α)、P53和P21的表达,流式细胞术检测细胞周期分布,CCK-8检测细胞增殖,克隆形成实验检测经X线照射后的细胞存活分数。结果:与常氧组相比,乏氧组AngⅡ表达显著上调(P<0.01),HIF-1α、P53和P21表达均上调,细胞周期G0/G1/S比例显著增加(P<0.05),细胞增殖无显著差异(P>0.05),但细胞存活分数显著增加(P<0.01)。用坎地沙坦处理乏氧A549细胞后,与乏氧组相比,坎地沙坦+乏氧组AngⅡ表达无显著差异(P>0.05),但HIF-1α、P53和P21表达均下调,细胞周期G0/G1/S比例显著降低(P<0.05),细胞增殖无显著差异(P>0.05),但细胞存活分数显著降低(P<0.01)。结论:坎地沙坦能增加乏氧条件下肺腺癌A549细胞放射敏感性,相关机制可能为坎地沙坦下调HIF-1α表达后抑制细胞周期G0/G1/S阻滞。

Objective:To investigate the effect of candesartan on the radiosensitivity of the lung adenocarcinoma A549 cells in the hypoxic condition and its mechanism.Methods:The A549 cells were divided into normoxia group,hypoxia group and candesartan combined with hypoxia group. The expression of angiotensin Ⅱ(AngⅡ)was detected by ELISA,the expression of Hypoxia inducible factor 1α(HIF-1α),P53 and P21 were detected by Western blot,the distribution of cell cycle was detected by flow cytometry,the cell proliferation was detected by CCK-8 assays,the cell surviving fraction(SF)of A549 cells treated with X-ray radiation was detected by colony formation assays.Results:Compared with the normoxia group,the expression of AngⅡ in the hypoxia group was significantly up-regulated(P<0.01),the expression of HIF-1α,P53 and P21 was up-regulated,while the proportion of G0/G1/S was significantly increased(P<0.05),the cell proliferation was no significant distinction,but the cell surviving fraction was significantly increased. After the hypoxia group was treated by candesartan,compared with the hypoxia group,the expression of AngⅡ in the candesartan combined with hypoxia group was no significant distinction(P>0.05),but the expression of HIF-1α,P53 and P21 was downregulated,the proportion of G0/G1/S was significantly decreased(P<0.05),the cell proliferation was no significant distinction(P>0.05),but the cell surviving fraction was significantly decreased(P<0.01).Conclusion:Candesartan can increase the radiosensitivity of the lung adenocarcinoma A549 cells in the hypoxic condition,the related mechanism may be that candesartan down-regulates the expression of HIF-1α and then inhibits the G0/G1/S cell cycle arrest.