缬沙坦对非小细胞肺癌H1299细胞放射敏感性的影响及作用机制  

Valsartan enhances radiosensitivity in non-small cell lung cancer by inhibiting SRSF1 expression and blocking the PI3K/AKT pathway

作　　者：孙强 闫英 SUN Qiang;YAN Ying(Department of Radiotherapy,General Hospital of Northern Theater Command,Shenyang 110016,China)

机构地区：[1]北部战区总医院放射治疗科,辽宁沈阳110016

出　　处：《解剖科学进展》2023年第5期490-493,498,共5页Progress of Anatomical Sciences

摘　　要：目的探究缬沙坦对非小细胞肺癌H1299细胞放射敏感性的影响及作用机制。方法采用0、1、10、20、30、40、50、100μmol/L的缬沙坦处理H1299细胞48 h,CCK-8检测各组细胞活性,筛选出最佳的缬沙坦抑制浓度用于后续实验。细胞分为DMSO对照组、缬沙坦组、IR组和缬沙坦+IR组。CCK-8检测各组细胞增殖情况;平板克隆形成实验检测细胞的克隆形成能力;流式细胞术检测细胞凋亡情况;Western blot检测凋亡相关蛋白Bax、Bcl-2、cleaved Caspase-3表达水平;Real-time PCR检测SRSF1 mRNA表达水平;Western blot检测细胞中p-PI3K、PI3K、p-AKT和AKT蛋白表达水平。结果40μmol/L为缬沙坦最佳处理浓度。缬沙坦和放疗单独处理均能使细胞增殖水平和克隆形成能力下降,凋亡率升高,SRSF1表达降低,p-PI3K和p-AKT磷酸化水平下降;缬沙坦和放疗共同处理能使细胞增殖水平和克隆形成能力进一步下降,细胞凋亡率进一步升高,SRSF1表达以及p-PI3K和p-AKT磷酸化水平进一步下降。结论缬沙坦通过抑制SRSF1表达抑制PI3K/AKT通路进而加强非小细胞肺癌放射敏感性。Objective To investigate the effect and mechanism of valsartan on radiosensitivity of non-small cell lung cancer H1299 cells.Methods H1299 cells were treated with 0,1,10,20,30,40,50,100μmol/L valsartan for 48 h,and the cell activity of each group was detected by CCK-8,and the optimal inhibitory concentration of valsartan was selected for subsequent experiments.The cells were divided into DMSO control group,valsartan group,IR group and valsartan+IR group.Cell proliferation was detected by CCK-8.The clonogenesis ability of the cells was detected by plate clone formation assay.The apoptosis was detected by flow cytometry.The expressions of apoptosis-related proteins Bax,Bcl-2 and cleaved Caspase-3 were detected by Western blot.The level of SRSF1 mRNA was detected by Real-time PCR.The expressions of p-PI3K,PI3K,P-AKT and AKT in cells were detected by Western blot.Results The optimal treatment concentration of valsartan was 40μmol/L.Both valsartan and radiotherapy alone could decrease cell proliferation and cloning capacity,increase apoptosis rate of cells,decrease the expressions of SRSF1,p-PI3K and p-AKT.The combination of valsartan and radiotherapy could further decrease the cell proliferation and clonogenesis,increase the apoptosis rate of cells,and decrease the expressions of SRSF1,p-PI3K and p-AKT.Conclusion Valsartan enhanced the radiosensitivity of non-small cell lung cancer by inhibiting the expression of SRSF1 and inhibiting the PI3K/AKT pathway.

关 键 词：非小细胞肺癌 缬沙坦 放疗敏感性 SRSF1 PI3K/AKT通路 

分 类 号：R734.2[医药卫生—肿瘤]