丁酸钠抑制人结肠癌细胞SW480上皮间质转化的机制

Sodium butyrate inhibits epithelial-mesenchymal transition in human colon cancer cell line SW480

目的:探讨丁酸钠(sodium butyrate,NaB)是否能够抑制人结肠癌细胞上皮间质转化(epithelium-mesenchymal transition,EMT)及其机制.方法:比较正常人结肠上皮细胞(human colon epithelium cell,HCoEpiC)与结肠癌细胞SW480间EMT标志物E-Cadherin、Vimentin的表达差异.再以0.2 mmol/L丁酸钠处理SW480 72 h,观察其迁移和侵袭能力的变化;Western blot检测EMT标志物E-Cadherin、Vimentin和缺氧诱导因子-1α(hypoxia-inducible factor-1α,HIF-1α)等蛋白浓度变化.结果:E-Cadherin在SW480中表达显著低于HCoEpiC;Vimentin在SW480中表达显著高于HCoEpiC,P<0.05.丁酸钠处理后SW480,迁移和侵袭能力明显下降,P<0.05.E-Cadherin在SW480实验组、对照组中相对含量分别为0.07±0.02和0.23±0.04,显著增高,P<0.05.Vimentin在SW480实验组、对照组中相对含量分别为0.32±0.05和0.17±0.03,显著降低,P<0.05.HIF-1α在实验组、对照组中相对含量分别为0.15±0.04和0.07±0.03,显著降低,P<0.05.结论:SW480与正常结肠上皮细胞相比发生了显著的EMT.丁酸钠可抑制SW480细胞的迁移和侵袭能力,可能是通过抑制HIF-1α,进而实现抑制人结肠癌细胞SW480的EMT.

AIM： To investigate whether sodium butyrate（NaB） inhibits epithelial-mesenchymal transition（EMT） in human colon cancer cells and the un-derlying mechanism.METHODS： The differential expression of EMTmarkers, E-Cadherin and Vimentin, betweenhuman colon epithelial cells（HCoEpiC） andcolon cancer cells（SW480） were compared. Theabilities of migration and invasion of SW480cells were assessed following treatment with 0.2 mmol/L NaB for 72 h. The relative expression levels of E-Cadherin, Vimentin and hypoxia-inducible factor-1α（HIF-1α） were determined by Western blot analysis. RESULTS： The relative expression level of E-Cadherin in SW480 cells was significantly lower than that in HCoEpiC cells; however, the expression level of Vimenin in SW480 cells was significantly higher than that in HCoEpiC cells（P 〈 0.05）. After treatment with NaB, the migration and invasion abilities of SW480 cells were signif-icantly inhibited（P 〈 0.05）. Following treatment with NaB, compared with the control group, treatment with NaB significantly up-regulated E-Cadherin expression（0.07 ± 0.02 vs 0.23 ± 0.04, P 〈 0.05）, and down-regulated Vimenin（0.32 ± 0.05 vs 0.17 ± 0.03, P 〈 0.05） and HIF-1α expres-sion（0.15 ± 0.04 vs 0.07 ± 0.03, P 〈 0.05） in SW480 cells. CONCLUSION： Compared with normal human colon epithelial cells, significant EMT occurs in SW480 cells. NaB can inhibit the abilities of mi-gration and invasion and EMT of SW480 cells, possibly through inhibition of HIF-1α expres-sion.