全反式维甲酸及其衍生物对乳腺癌细胞株MDA-MB-231凋亡的影响

目的：研究全反式维甲酸( ATRA)及其衍生物4-氨基-2-三氟甲基苯基维甲酸酯( ATPR)对人乳腺癌细胞MDA-MB-231体外凋亡的影响。方法不同浓度ATRA及其衍生物ATPR分别处理MDA-MB-231细胞48 h后,Hoechst染色及流式细胞术检测细胞凋亡的变化,RT-PCR检测凋亡蛋白Caspase-3 mRNA水平的变化, Western blot法检测相关凋亡蛋白表达水平的变化。结果与ATRA相比,相同浓度的ATPR能明显促进MDA-MB-231细胞的凋亡,随着浓度的增加,凋亡作用越加显著( P<0．05)。 RT-PCR显示 ATPR作用后Caspase-3 mRNA 水平显著上调( P <0．05)。 Western blot法显示ATPR能下调抗凋亡蛋白Bcl-2、NF-κB、survivin的表达( P<0．05) ,上调促凋亡蛋白Bax、Grim-19、Caspase-3的表达(P<0．05)。结论 ATPR比ATRA更明显地促进人乳腺癌细胞MDA-MB-231的凋亡。

The influence of ATRA and its derivative on the cell apoptosis of breast cancer cell line MDA-MB-231

Objective To investigate the influence of all-trans retinoic acid ( ATRA) and its derivative 4-amino-2-trifluoromethyl-phenyl ester (ATPR) on the apoptosis of breast cancer cell line MDA-MB-231. Methods MDA-MB-231 was treated with different concentrations of ATRA and ATPR for 48 h. Hoechst staining and flow cytometry were used to observe cell apoptosis. The mRNA level of apoptosis-related protein Caspase-3 was analyzed by RT-PCR. Western blot was performed to detect the expression of apoptosis-related proteins. Results Compared with ATRA, the same concentrations of ATPR promoted the apoptosis of MDA-MB-231 more obviously(P<0. 05), and the effect was dose-dependent. RT-PCR showed ATPR significantly raised the mRNA level of Caspase-3 ( P <0. 05 ) . Western blot displayed that ATPR decreased the expression of anti-apoptotic protein such as Bcl-2 , NF-κB, survivin(P <0. 05) and increased the expression of pro-apoptotic protein Bax, Grim-19, Caspase-3(P <0. 05). Conclusion Contrasted to ATRA, ATPR is able to promote the cell apoptosis of MDA-MB-231 more markedly.