促性腺激素释放激素类似物对人乳腺癌细胞的影响

Effect of gonadotropin-releasing hormone analogue on human breast cancer cell line in vitro

目的:探讨促性腺激素释放激素(gonadotropin-releasing hormone,GnRH)类似物曲普瑞林(triptorelin)对人乳腺癌细胞株MCF-7、MDA-MB-231细胞生长及细胞外信号调节蛋白激酶(extracellular signal-regulated kinase,ERK)/丝裂原活化蛋白激酶(mitogen-activated protein kinases,MAPK)和磷脂酰肌醇-3-激酶(phosphatidylinositol-3-kinase,PI3K)/蛋白激酶B(protein kinase B,Akt)信号通路中重要信号分子ERK1/2和Akt活化的影响。方法:使用不同浓度、不同时间的曲普瑞林刺激人乳腺癌MCF-7及MDA-MB-231细胞株,MTT法检测细胞增殖,流式细胞术检测细胞周期的分布,Western blotting检测Akt和ERK1/2的磷酸化程度。结果:曲普瑞林(10-5mol/L)作用人乳腺癌MCF-7细胞192 h、曲普瑞林(10-4mol/L)作用人乳腺癌MCF-7细胞168 h、192 h或曲普瑞林(10-4mol/L)作用人乳腺癌MDA-MB-231细胞192 h可明显抑制细胞生长(P<0.05);曲普瑞林(10-4mol/L)作用人乳腺癌MCF-7和MDA-MB-231细胞192 h,ERK1/2的磷酸化程度均较正常对照组低,Akt的磷酸化程度较正常对照组高,但差异无统计学意义(P>0.05)。结论:GnRH类似物曲普瑞林对人乳腺癌细胞的抑制作用,不仅仅是通过对垂体激素的降调节机制,还可能产生直接抑制作用。但该抑制作用未涉及ERK/MAPK和PI3K/Akt信号通路。

AIM：To investigate the effects of gonadotropin-releasing hormone （ GnRH） analogue on the growth of breast cancer cell lines MCF-7 and MDA-MB-231 in vitro and to explore the related mechanisms with PI 3K/Akt or ERK/MAPK pathways .METHODS： The proliferation of human breast cancer cell lines MCF-7 and MDA-MB-231 treatment with triptorelin was detected by MTT assay and the distribution of the cell cycle was determined by flow cytometry .The phosphorylation of the ERK 1/2 and Akt was evaluated by Western blotting .RESULTS：Triptorelin inhibited the prolifera-tion of MCF-7 cells at concentration of 10-5 mol/L after treated for 192 h or at concentration of 10 -4 mol/L after treated for 168 h and 192 h.Triptorelin inhibited the proliferation of MDA-MB-231 cells at concentration of 10 -4 mol/L after treated for 192 h （P〈0.05）.Treatment with triptorelin for 192 h at concentration of 10 -4 mol/L had no statistical significance effect on phosphorylation of ERK1/2 and Akt（P＆gt;0.05）.CONCLUSION：Inhibitory effect of GnRH analogue triptorelin on human breast cancer cells is not just the connection with the down-regulation of pituitary hormone , but also a direct in-hibitory effect.The role may not be involved in the activation of ERK /MAPK and PI3K/Akt signaling pathways .