SOX2表达变化对非小细胞肺癌A549细胞紫杉醇敏感性的影响及其机制  

Effect and mechanism of SOX2 expression changes on paclitaxel sensitivity in non-small-cell lung cancer A549 cells

作　　者：胡莎莎[1] 黎克秀 张威 HU Shasha;LI Kexiu;ZHANG Wei(Department of Respiratory and Critical Care Medicine,Pukou People's Hospital of Nanjing(Pukou Branch of Jiangsu Provincial People's Hospital),Nanjing 211800,China;不详)

机构地区：[1]南京市浦口人民医院(江苏省人民医院浦口分院)呼吸与危重症医学科,江苏南京211800 [2]南京医科大学第四附属医院呼吸与危重症医学科,江苏南京211800

出　　处：《山东医药》2025年第2期46-50,共5页Shandong Medical Journal

摘　　要：目的观察性别决定基因相关转录因子2(SOX2)表达变化对人非小细胞肺癌细胞株A549紫杉醇(PTX)敏感性的影响,并基于氯离子电压门控通道3(ClC-3)调控探讨相关机制。方法培养A549细胞,采用逐步增加PTX剂量间歇作用的方法诱导对PTX耐药的A549细胞株(A549/R);采用MTT实验检测A549、A549/R细胞对PTX的敏感性并测算半数抑制浓度(IC50),采用Western blotting法检测耐药相关蛋白(ABCC2、ABCC10C、MDR1)、SOX2蛋白、ClC-3蛋白,采用qRT-PCR法检测SOX2、ClC-3 mRNA。分别将SOX2敲低质粒、SOX2过表达质粒及SOX2过表达质粒+ClC-3敲低质粒转染A549细胞,检测转染细胞与未转染细胞中的ClC-3 mRNA及蛋白,并测算PTX的IC50。结果PTX作用于A549-R细胞的IC50高于A549细胞(P<0.01);A549-R细胞中ABCC2、ABCC10C、MDR1、SOX2、ClC-3蛋白及SOX2、ClC-3 mRNA表达高于A549细胞(P均<0.01)。SOX2低表达A549细胞ClC-3 mRNA、蛋白表达及PTX的IC50低于A549细胞(P均<0.05);SOX2过表达A549细胞ClC-3 mRNA、蛋白表达及PTX的IC50高于A549细胞(P均<0.05);SOX2过表达+ClC-3低表达A549细胞PTX的IC50与A549细胞差异无统计学意义(P>0.05)。结论PTX耐药的A549细胞中SOX2表达增高,SOX2对A549细胞PTX敏感性的调控作用可能与调节ClC-3表达有关。Objective To observe the effect of changes in the expression of sex-determining region Y-box2(SOX2)on the sensitivity of human non-small-cell lung cancer cell line A549 to paclitaxel(PTX),and to explore the relevant mechanism based on the regulation of voltage-gated chloride channel-3(ClC-3).Methods We cultivated A549 cells and induced PTX-resistant A549 cell line(A549/R)by gradually increasing the dosages of PTX intermittently.MTT assay was used to detect the sensitivity of A549 and A549/R cells to PTX and we calculated the half maximal inhibitory concen tration(IC50).Western blotting was used to detect resistance-related proteins(ABCC2,ABCC10C,and MDR1),SOX2 protein,and ClC-3 protein.The qRT-PCR was used to detect SOX2 ClC-3 mRNA.We transfected A549 cells with SOX2 knockdown plasmid,SOX2 overexpression plasmid,and SOX2 overexpression plasmid+ClC-3 knockdown plasmid,respectively,detected ClC-3 mRNA and protein in transfected and untransfected cells,and calculated the IC50 of PTX.Results The IC50 of PTX on A549-R cells was higher than that on A549 cells(P<0.01);the expression levels of ABCC2,ABCC10C,MDR1,SOX2,ClC-3 proteins and SOX2,ClC-3 mRNA in A549-R cells were higher than those in A549 cells(all P<0.01).The expression levels of ClC-3 mRNA and protein,and the IC50 of PTX in A549 cells with low SOX2 expression were lower than those in A549 cells(all P<0.05);the expression levels of ClC-3 mRNA and protein,and the IC50 of PTX in A549 cells with SOX2 overexpression were higher than those in A549 cells(all P<0.05);there was no significant difference in the IC50 of PTX between A549 cells with overexpression of SOX2 and low expression of ClC-3 and A549 cells(P>0.05).Conclusion SOX2 expression increased in A549 cells resistant to PTX,and the regulatory effect of SOX2 on PTX sensitivity in A549 cells may be related to the regulation of ClC-3 expression.

关 键 词：非小细胞肺癌 紫杉醇 细胞耐药 性别决定基因相关转录因子2 氯离子电压门控通道3 

分 类 号：R734.2[医药卫生—肿瘤]