细胞内Ca^(2+)在HMG-CoA还原酶抑制剂抑制MCF-7细胞增殖中的作用

Role of intracellular calcium in proliferation inhibition of MCF-7 cells induced by HMG-CoA reductase inhibitor

目的 探讨HMG CoA还原酶抑制剂洛伐他汀 (LOV)对人乳腺癌MCF 7细胞增殖功能和细胞内游离Ca2 + 浓度([Ca2 + ]i)变化的影响。方法 4、8、16μmol LLOV处理MCF 7细胞 1～ 3d后 ,MTT比色法检测细胞增殖功能 ,流式细胞仪测定细胞周期相的分布及凋亡率 ,激光共聚焦显微技术观察细胞 [Ca2 + ]i变化以及RT PCR方法分析LOV对MCF 7细胞质膜钙泵PMCA1mRNA表达的影响。结果 LOV对MCF 7细胞增殖有明显的抑制作用 ,并使细胞的生长阻滞于G0 G1 期 ,该作用存在一定的剂量和时间关系 ,但其诱导MCF 7细胞凋亡的作用不明显 ;同时LOV可持续升高MCF 7细胞 [Ca2 + ]i,但对MCF 7细胞质膜钙泵PMCA1mRNA表达无明显影响。结论 LOV导致的 [Ca2 + ]i持续升高可能与LOV影响MCF 7质膜PMCA1功能有关 ;[Ca2 + ]i的升高及相关信号通路的变化可能参与了LOV对MCF

Objective To study the effects of HMG CoA reductase inhibitor, lovastatin (LOV), on the proliferation of human breast cancer cell MCF 7 and the role of intracellular calcium concentration ([Ca 2+ ]i) in this event. Methods After treated with LOV at the dosages of 4, 8 and 16 μmol/L for 1-3 d respectively, the proliferation of MCF 7 cells was examined with MTT, and the distributions of cell cycles with FCM assay. Meanwhile, the change of [Ca 2+ ]i of MCF 7 cells was observed with laser scanning confocal microscopy, and the expression of plasma membrane calcium ATPase isoform 1 (PMCA1) mRNA with RT PCR. Results Lovastatin, inhibited the proliferation of MCF 7 cells and arrested MCF 7 cells in the G 0/G 1 phase of cell cycle, in a dose and time dependent manner. However, apoptosis of LOV treated MCF 7 cells was not obvious. Simultaneously, LOV increased [Ca 2+ ]i of MCF 7 cells, but didn't change the expression of PMCA1 mRNA. Conclusion The results suggest that LOV has the capabilities of inhibiting the proliferation of MCF 7 cells and arresting them in G 0/G 1 phase. These effects of LOV maybe correlate with LOV changing the function of PMCA1and increasing [Ca 2+ ]i of MCF 7 cells.