xCT影响肝癌细胞转移的作用机制研究

目的：探讨人类肝细胞癌中xCT（氨基酸转运系统system xc-的功能性亚基）的表达对于自噬、EMT（上皮细胞间质化）和肿瘤细胞转移的影响.方法：用Western Blot和RT-PCR方法检测肿瘤细胞在xCT抑制剂SASP（柳氮磺胺毗啶）的作用下,其自噬和EMT过程相关基因的表达水平的改变.伤口愈合实验和Transwell分析xCT在受到抑制后,肿瘤细胞迁移能力的改变.结果：SASP处理过的97H人类高转移肝癌细胞与对照组相比,自噬相关蛋白LC3和Beclin1表达升高,EMT的标志物E-cadherin表达升高,Vimentin的表达降低,参与EMT过程的重要转录因子Snail表达降低.结论：抑制xCT的表达可以使人类高转移肝癌细胞发生自噬,降低转录因子Snail的表达,从而减弱EMT过程的发生并降低人类高转移肝癌细胞的转移能力.

Molecular mechanism of metastasis in hepatocellular carcinoma inhibited by xCT

Objective： To discuss the influence of xCT expression on EMT （epithelial-mesenchymal transition） and tumor matastasis in hepatocellular carcinoma. Methods： Western Blot and RT-PCR were used to detect the expression levels of autophagy and EMT related gene after treated with sulfasalazine （SASP）, an inhibitor of xCT activity. Wound healing assay and transwell assay were performed to evaluate the disruption effect of xCT on cell motility. Results：The expression levels of autophagy related protein LC3 and Beclin 1 were elevated in SASP treated 97H cells compared with in control 97H cells. E-cadherin was upregulated whereas Vimentin was downregulated when xCT was deficient. Both E-cadherin and Vinmentin were markers of EMT process. Conclusion： xCT disruption can activate autophagy and attenuate EMT, and eventually suppress cell migration.