基于CYP19探讨雷公藤甲素抗ER(+)人乳腺癌MCF-7细胞作用机理

目的 基于CYP19基因阐明雷公藤甲素抗ER(+)人乳腺癌细胞的作用机制。方法 雷公藤甲素组与来曲唑组相对照，采用MTT法观察雷公藤甲素对MCF-7细胞增殖的影响；采用Western blot观察其对芳香化酶的影响；采用RT-PCR观察其对CYP19基因的影响；采用瞬时转染形成高表达及低表达CYP19基因的MCF-7细胞，并用Western blot的方法观察雷公藤甲素对转染细胞CYP19以及其下游通路相关基因JNK、P38和ERK的影响。结果 雷公藤甲素能明显抑制MCF-7细胞增殖（P<0.01），其抑制作用随着浓度增高和时间的延长而增强，能抑制芳香化酶及CYP19基因的表达，并能明显下调低表达CYP19-MCF-7细胞的CYP19表达，及抑制JNK、p-38和ERK的磷酸化。结论 雷公藤甲素抗MCF-7细胞的作用机制之一，是通过抑制芳香化酶起作用，并引起下游Ras-Raf-MAPK-ERK激酶系统通路受抑制。 

Study on Antiblastic Effect Mechanism of ER(+) Human Breast Cancer MCF-7 Cells by Triptolide Based on CYP19

OBJECTIVE To investigate the mechanisms of Triptolide in ER(+) human breast cancer MCF-7 cells from CYP19. METHODS The inhibition of the MCF-7 cells influenced by Triptolide and Letrozole was analyzed respectively by MTT assays. The aromatase levels were measured by Western blot. The CYP19 gene was observed by RT-PCR. The MCF-7 cells of high and low expression CYP19 gene were transfacted. It's CYP-19 and downstream channel gene JNK，p-38 and ERK were observed by Western blot. RESULTS Triptolide displayed a dose- and time-dependent inhibition of the MCF-7 cells. It inhibited the aromatase and CYP19. The expression of CYP19 in MCF-7 cells of low expression CYP19 was significantly decreased.Phosphorylation of JNK，p38 and ERK was inhibited too. CONCLUSION Triptolide inhibit MCF-7 cells not only via inhibition aromatase， but also blocking Ras-Raf-MAPK-ERK enzyme.