实用临床医药杂志2024，Vol.28Issue(23)：20-26,7.DOI:10.7619/jcmp.20241561
SLC1A5-TM4SF1复合物对食管鳞状细胞癌细胞顺铂耐药的调控作用及机制
Regulating effect and mechanism of SLC1A5-TM4SF1 complex on cisplatin resistance in esophageal squamous cell carcinoma cells
摘要
Abstract
Objective To investigate the regulatory effect and molecular mechanism of solute carrier family 1 member 5(SLC1A5)-tetraspanin superfamily member 1(TM4SF1)complex on cis-platin resistance in esophageal squamous cell carcinoma(ESCC)cells.Methods SLC1A5-overex-pressing Eca109 cells were constructed using lentiviral vectors,and the effect of SLC1A5 on cisplatin sensitivity was assessed through cell viability assays.Western blotting(WB)was employed to detect SLC1A5 expression in Eca109 cells and cisplatin-resistant Eca109 cells(Eca109-R).SLC1A5 expression was knocked down in Eca109-R cells using lentiviral vectors,and cisplatin sensitivity was examined thereafter.Quantitative real-time polymerase chain reaction(qRT-PCR)was utilized to analyze the influence of SLC1A5 knockdown on the expression of key genes involved in DNA damage repair in Eca109-R cells.In SLC1A5-knockdown Eca109-R cells,cell viability assays were performed to e-valuate the sensitivity to cisplatin after RAD50 overexpression.Additionally,Eca109 cells were sep-arately or co-overexpressed with SLC1A5 and TM4SF1 using lentiviral vectors,and the effect of the SLC1A5-TM4SF1 complex on RAD50 expression and cisplatin resistance was examined through cell viability assays.Results Compared with control cells,Eca109 cells overexpressing SLC1A5 exhib-ited enhanced cisplatin resistance(P＜0.05).Eca109-R cells showed increased SLC1A5 protein expression,and knockdown of SLC1A5 cells were more sensitivity to cisplatin(P＜0.05).RAD50 gene expression was significantly downregulated upon SLC1A5 knockdown under cisplatin treatment(P＜0.05).Knockdown of SLC1A5 inhibited RAD50 protein expression,and overexpression of RAD50 in SLC1A5-knockdown cells significantly restored cisplatin resistance(P＜0.05).Co-over-expression of SLC1A5 and TM4SF1 can further up-regulate the expression of RAD50,and the drug resistance of the cells to cisplatin was enhanced compared with the control cells(P＜0.05).Con-clusion The SLC1A5-TM4SF1 complex promotes cisplatin resistance in ESCC cells by upregulating RAD50 expression.关键词
氨基酸转运载体溶质载体家族1成员5/四跨膜蛋白超家族成员1/RAD50双链断裂修复蛋白/食管鳞状细胞癌/耐药/膜蛋白复合物Key words
molecular mechanism of solute carrier family 1 member 5/tetraspanin superfam-ily member 1/RAD50 double-strand break repair protein/esophageal squamous cell carcinoma/drug resistance/membrane protein complex分类
医药卫生引用本文复制引用
孙云,王远志,赵恬恬,廖月霞,杭庆雷..SLC1A5-TM4SF1复合物对食管鳞状细胞癌细胞顺铂耐药的调控作用及机制[J].实用临床医药杂志,2024,28(23):20-26,7.基金项目
国家自然科学基金青年科学基金资助项目(32201047) （32201047）
中国博士后科学基金面上资助项目(2023M741447) （2023M741447）
