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作 者:许琮[1] 夏超[1] 张淑娟[1] 覃华[1] 李德民[1] 赵秋[1]
机构地区:[1]华中科技大学同济医学院附属同济医院消化内科,湖北省武汉市430030
出 处:《世界华人消化杂志》2015年第24期3831-3837,共7页World Chinese Journal of Digestology
基 金:武汉市科技局应用基础基金资助研究项目;No.2014060101010052~~
摘 要:目的:观察盐霉素对胰腺癌C a p a n-2及PA N C-1细胞增殖及迁徙能力的影响,探讨其抑制细胞迁移能力的可能作用机制.方法:以1、2、4、8、10、20、40、60、80?m o l/L不同浓度的盐霉素处理C a p a n-2及PA N C-1细胞24 h后,利用C C K8检测细胞增殖并得出半数抑制率的药物浓度(50%inhibitory concentration of a substance,I C50).利用Tr a n s w e l l实验检测细胞迁移能力的改变,进一步分别利用Western blot及Real-time PCR检测上皮间质转化(epithelialm e s e n c h y m a l t r a n s i t i o n,E M T)关键分子E-cadherin及Vimentin的表达变化.结果:盐霉素呈浓度依赖性抑制Capan-2及PA N C-1细胞的增殖,其I C50分别为20及10?mol/L.Transwell细胞迁移实验发现盐霉素可明显抑制细胞的迁移能力(P值均<0.05),Western blot实验发现E-cadherin表达上调而Vimentin表达下调,进而Real-time PCR检测后发现Capan-2细胞在DMSO对照组作用及盐霉素处理后E-cadherin基因m RNA的相对表达量分别为1.2140±0.0988 vs 3.7920±0.0733,而Vimentin基因m RNA的相对表达量分别为0.9998±0.0332 vs 0.2756±0.1250;PANC-1细胞在DMSO对照组作用及盐霉素处理后E-cadherin基因m RNA的相对表达量分别为0.1210±0.1130 vs 0.5790±0.2230而Vi m e n t i n基因的m R N A相对表达量分别为3.9820±0.2670 vs 1.6920±0.0130,差异均有统计学意义(均P<0.05).结论:盐霉素可以抑制胰腺癌细胞体外增殖及迁徙能力,可能通过抑制EMT发生过程抑制细胞的转移能力.AIM:To investigate the effect of salinomycin on proliferation and migration of pancreatic cancer cell lines Capan-2 and PANC-1 and the possible mechanisms of inhibition of cell migration.METHODS:Canpan-2 and PANC-1 cells were treated with different concentrations of salinomycin for 24 h,while the cells treated with dimethyl sulphoxide(DMSO) were used as controls.Cell proliferation and the half maximal inhibitory concentration(IC50) of salinomycin were measured by CCK8 assay.Transwell assay was used to measure the migration of these cells which were pretreated with salinomycin at a concentration of IC50.The protein and mRNA expression of biomarkers for epithelialmesenchymal transition(EMT) was detected by Western blot and Real-time PCR,respectively.RESULTS:Salinomycin inhibited the proliferation of Capan-2 and PANC-1 cells in a dosedependent manner.The IC50 values for Capan-2and PANC-1 cells were 20 μmol/L and 10 μmol/L,respectively.Salinomycin significantly decreased the migration ability of pancreatic cancer cells as revealed by Transwell migration assay(P 〈0.05).The protein expression of E-cadherin was increased while that of Vimentin was decreased after salinomycin treatment.The expression of E-cadherin mRNA was increased in both Capan-2 and PANC-1 cells(P 〈0.05),while the expression of Vimentin mRNA was decreased in both Capan-2 and PANC-1 cells(P 〈0.05).CONCLUSION:Salinomycin can inhibit the proliferation and migration of Capan-2and PANC-1 cells possibly by inhibiting the process of EMT.
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