白黎芦醇对垂体腺瘤GH3细胞的抑制作用

Inhibitory effect of resveratrol in pituitary GH3 cells.

目的 探讨选择性雌激素受体调节剂白黎芦醇对垂体腺瘤GH3细胞中电压依赖性K+电流(IK(V) )和细胞增殖的影响。方法 不同浓度白黎芦醇作用GH3细胞,应用MTT比色法测定细胞增殖,流式细胞仪检测细胞周期分布,运用全细胞膜片钳技术记录和分析白黎芦醇对GH3细胞中IK(V)的作用。结果 白黎芦醇作用GH3细胞 3d后,以浓度效应关系抑制GH3细胞增殖,并使细胞增殖周期中G0 /G1 期阻滞,S期和G2 /M期百分率降低。全细胞膜片钳结果显示,白黎芦醇以浓度和时间效应抑制IK(V)。结论 白黎芦醇抑制GH3细胞增殖可能是通过阻断电压依赖性K+通道起作用。提示可应用选择性抗雌激素药物治疗垂体腺瘤。

Objective Resveratrol(RE), a natural phytoestrogen found in grapes and wine, has been reported to have a variety of health benefit properties. However, little is known of its mechanisms of action on ionic currents in pituitary tumor. We investigated its effect of voltage-dependent K+ current(I K(V))and cell proliferation on GH3 cells derived from the radiation-induced rat pituitary tumor. Methods GH3 cells were treated with RE(10μmol/L, 50μmol/L and 100μmol/L RE). The effect of RE on cell proliferation, distribution of cell cycle and I K(V) in GH3 cell were investigated with the aid of MTT assay, flow cytometry and the whole-cell patch-clamp technique respectively. Results After RE treatment for three days, RE decreased cell proliferation in a concentration-dependent manner with an IC 50 value of 50μmol/L.G 0/G 1 phase in cell proliferating cycle was blocked and cell proportion in the S and G 2/M phase decreased significantly. In whole-cell recording experiments, RE caused an inhibition of I K(V) in a concentration-and time-dependent manner. Conclusions The antiproliferative activity of RE may be partially explained by blockade of voltage-dependent K+ channel present in GH3 cells. These results indicate a role for selective antiestrogen agents in treating pituitary adenomas.