ITGA3对非小细胞肺癌紫杉醇耐药性的影响及机制  

Effect and mechanism of ITGA3 on paclitaxel resistance in non-small-cell lung cancer

作　　者：蔡恒[1] 林峰[1] 宋淦[1] 赵和平 夏小兵 CAI Heng;LIN Feng;SONG Gan;ZHAO Heping;XIA Xiaobing(Department of Thoracic Surgery,Macheng People's Hospital,Macheng 438300,China)

机构地区：[1]麻城市人民医院胸外科,湖北麻城438300

出　　处：《山东医药》2024年第28期48-52,共5页Shandong Medical Journal

基　　金：麻城市人民医院科研项目(KY-Y-2022B01)。

摘　　要：目的探讨整合素亚单位α3(ITGA3)对非小细胞肺癌(NSCLC)紫杉醇耐药性的影响及机制。方法选取行紫杉醇联合顺铂化疗的50例NSCLC患者肿瘤组织及A549/Tax(人肺腺癌紫杉醇耐药性)细胞、人A549细胞株及人胚胎肺成纤维细胞(MRC-5),RT-qPCR法检测组织及细胞中ITGA3基因mRNA表达;以A549/Tax细胞为研究对象,分别转染pcDNA3.1-ITGA3质粒(oe-ITGA3)及pcDNA3.1空载体(oe-NC)、沉默ITGA3小RNA(sh-ITGA3)及阴性对照(sh-NC),标记为oe-ITGA3组、oe-NC组、sh-ITGA3组、sh-NC组,同时以未经处理的A549/Tax细胞为对照组;CCK-8法检测24、48 h的OD450值;Western blotting法检测上皮间质转化(EMT)相关蛋白[波形蛋白(Vimentin)、钙黏附蛋白E(E-cadherin)、snail]及转化生长因子β(TGF-β)、免疫逃逸蛋白[程序性死亡分子配体1(PD-L1)]表达;RT-qPCR法检测A549/Tax细胞中ITGA3 mRNA表达;Transwell实验检测A549/Tax细胞迁移、侵袭能力。结果治疗后肿瘤组织中ITGA3 mRNA表达高于治疗前肿瘤组织(P<0.05),A549细胞、A549/Tax细胞中ITGA3 mRNA表达高于MRC-5细胞(P均<0.05)。治疗后,NSCLC患者肿瘤组织中Vimentin、snail、TGF-β、PD-L1较治疗前增加,E-cadherin降低(P均<0.05)。与对照组、oe-NC组相比,oe-ITGA3组24、48 h的OD450值、细胞迁移、侵袭数目、ITGA3 mRNA、Vimentin、snail、TGF-β、PD-L1表达增加,E-cadherin表达降低(P均<0.05);与对照组、sh-NC组相比,sh-ITGA3组24、48 h OD450值、细胞迁移、侵袭数目、ITGA3 mRNA、Vimentin、snail、TGF-β、PD-L1表达降低,E-cadherin表达增加(P均<0.05)。结论下调ITGA3表达可抑制NSCLC细胞对紫杉醇的耐药性,其机制可能与抑制TGF-β表达有关。Objective To study the effect of integrin subunitα3(ITGA3)on paclitaxel resistance in non-small-cell lung cancer(NSCLC)and its mechanism.Methods Tumor tissues from 50 NSCLC patients treated with paclitaxel com-bined with cisplatin chemotherapy,A549/Tax(paclitaxel-resistant human lung adenocarcinoma)cells,human A549 cell line and human embryonic lung fibroblasts(MRC-5)were selected.RT-qPCR was used to detect the expression levels of ITGA3 mRNA in tissues and cells.A549/Tax cells were used as the research objects and were transfected with pcDNA3.1-ITGA3 plasmid(oe-ITGA3)and pcDNA3.1 empty vector(oe-NC),silencing ITGA3 small RNA(sh-ITGA3)and nega-tive control(sh-NC),respectively,which were recorded as the oe-ITGA3 group,oe-NC group,sh-ITGA3 group and sh-NC group,respectively.Untreated A549/Tax cells were used as the control group.CCK-8 was used to detect the OD450 val-ues at 24 and 48 h.Western blotting was used to detect the expression of EMT-related proteins[vimentin,E-cadherin,snail,]and TGF-β,and immune escape protein[programmed death ligand-1(PD-L1)];RT-qPCR was used to detect the expression of ITGA3 mRNA in A549/Tax cells;Transwell assay was used to detect the migration and invasion abilities of A549/Tax cells.Results After treatment,the expression of ITGA3 mRNA in the tumor tissues was higher than that be-fore treatment(P<0.05).The expression levels of ITGA3 mRNA in the A549 cells and A549/Tax cells were higher than that in the MRC-5 cells(all P<0.05).After treatment,Vimentin,snail,TGF-βand PD-L1 in the tumor tissues of NSCLC patients increased in comparison with those before treatment,while E-cadherin decreased(all P<0.05).Compared with the control group and the oe-NC group,the OD450 values at 24 and 48 h,the number of cell migration and invasion,the IT-GA3 mRNA expression,the expression levels of Vimentin,snail,TGF-βand PD-L1 increased,and the expression of E-cadherin decreased in the oe-ITGA3 group(all P<0.05).Compared with the control group and the sh-NC group,the OD450 values at 24 and 48 h,the numbe

关 键 词：非小细胞肺癌 上皮间质转化 整合素亚单位α3 紫杉醇 耐药性 

分 类 号：R734.2[医药卫生—肿瘤]