全反式维甲酸通过ERK1/2信号途径抑制结肠癌细胞株的增殖

All-trans retinoic acid( ATRA) inhibit proliferation of colon cancer cell lines by extracellular regulated protein kinases 1 and 2 (ERK1/2) signal pathway

目的:探讨全反式维甲酸(All-trans retinoic acid,ATRA)是否通过作用ERK1/2信号通路抑制结肠癌细胞增殖。方法:MTT法检测ATRA对结肠癌细胞株的增殖作用,RT-PCR及Western blot法检测ATRA处理的LS174T细胞中MEK1/2/ERK1/2的表达水平。流式细胞仪测定经ATRA与PD98059(MEK1/2的特异性抑制剂)联合处理后的LS174T细胞的凋亡水平。结果:MTT生长曲线显示ATRA能抑制结肠癌LS174T细胞株增殖,RT-PCR及Western blot结果表明ATRA可以提高ERK mRNA及蛋白的表达水平,促进ERK磷酸化。PD98059与ATRA联用,部分降低结肠癌细胞p-ERK表达,但增强ATRA诱导结肠癌细胞凋亡作用。结论:ATRA可以抑制结肠癌细胞增殖,其对肿瘤的诱导凋亡作用可能是通过包含MEK/ERK信号途径在内的多条信号通路进行的。

Objective：To explore whether all-trans retinoic acid （ATRA） inhibits proliferation of colon cancer cell by acting ERK1/2 signal pathway. Methods： ATRA on the proliferation of colon cancer cell lines were detected by MTY assay, RT-PCR and Western blot assay were used to detect MEK1/2/ERK1/2 expression levels of LS174T cells treated by ATRA. LS174T cells apoptosis levels were measured by flow cytometry after combined treatment of ATRA and PD98059 （MEK1/2 specific inhibitor）. Results： MTI＇ growth curve showed that ATRA could inhibit the proliferation of colon cancer cell line LS174T. RT-PCR and Western blot results showed that ATRA could increase expression levels of ERK mRNA and protein, and could promote ERK phosphorylation. Combination of PD98059 and ATRA lowered some p-ERK expressions in colon cancer cells, but meanwhile enhanced ATRA-induced apoptosis. Conclusion： ATRA can inhibit proliferation of colon cancer cell, and its induction of apoptosis of tumor may be conducted by muhiple signal pathways, including MEK/ERK.