高表达SLC2A1介导非小细胞肺癌顺铂耐药

Overexpressed SLC2A1 mediated cisplatin resistance on non-small cell lung cancer

目的探讨溶质载体家族2成员1(solute carrier family 2,member 1,SLC2A1)在非小细胞肺癌(non-small cell lung cancer,NSCLC)化疗耐药性中的作用。方法通过oncomine、GEPIA、HPA、GEO等数据库或在线分析工具分析SLC 2A1在NSCLC及顺铂耐药性NSCLC细胞系的表达;通过String结合DAVID 6.8分析SLC 2A1互作基因的通路富集;运用Coremine工具进行文本挖掘分析SLC 2A1介导NSCLC化疗耐药性的生物过程;通过Kaplan Meier-plotter分析SLC 2A1表达量与NSCLC患者总生存期(overall survival,OS)的相关性,以及SLC 2A1表达量与NSCLC化疗患者生存期的相关性;通过RT-PCR及Western blot法检测SLC2A1在顺铂敏感或耐药性NSCLC细胞系中的表达;MTT法结合caspase 3活性检测分析顺铂耐药NSCLC细胞系的凋亡情况。结果SLC2A1在NSCLC患者及顺铂耐药性的NSCLC细胞系中的显著升高,而且与患者的总生存期显著相关;顺铂耐药NSCLC细胞系高表达SLC2A1抑制了顺铂诱导的癌细胞凋亡,HIF-1信号通路、癌症中心碳代谢途径在SLC2A1互作基因中具有显著性富集。结论高表达SLC2A1通过抑制凋亡介导NSCLC顺铂耐药性。

Objective To explore the role of SLC2A1 on non-small cell lung cancer chemotherapy resistant.Methods oncomine,GEPIA,HPA,GEO databases or online tools were used to explore the expression of SLC2A1 on NSCLC or cisplatin resistant NSCLC cell line.Pathway enrichment analysis of SLC2A1 interacted genes was conducted by STRING and DAVID 6.8.RT-PCR and western blot were used to detect SLC2A1 expression in cisplatin sensitive or resistant NSCLC cell lines.MTT assay and caspase 3 The relation of SLC2A1 expression or microRNA expression and NSCLC OS were conducted by Kaplan Meier-plotter.COREMINE was used to analyzed the biological process of SLC2A1 mediated NSCLC chemotherapy resistance.Results SLC2A1 were over expressed in NSCLC and cisplatin resistant NSCLC cell line.High expression of SLC2A1 was significantly associated with lower OS in NSCLC.overexpression of SLC2A1 inhibited cisplatin mediated apoptosis in cisplatin resistant NSCLC cell line.HIF-1 signaling pathway,and Central carbon metabolism in cancer were enriched among genes interacted with SLC2A1.Conclusion Overexpressed SLC2A1 mediated NSCLC cisplatin resistance by inhibited apoptosis.