阻断MAPK通路对前列腺癌细胞增殖的影响

Blocking of the mitogen activated protein kinase signal transduction pathway inhibits the proliferation in the prostate cancer cells

目的:研究前列腺癌进展中细胞丝裂原活化蛋白激酶(MAPK)信号通路的变化,探讨阻断此通路对前列腺癌细胞增殖的影响。方法:用MTT法检测表皮生长因子(EGF)、PD98059对前列腺癌细胞系LNCaP、PC-3和DU145增殖的影响;用Western blot法检测细胞外信号调节激酶1/2(ERK1/2)表达和磷酸化ERK1/2水平的差异,以及EGF、PD98059对细胞ERK1/2磷酸化水平的影响。结果:EGF促进LNCaP、PC-3和DU145的增殖,PD98059抑制细胞增殖;Western blot结果显示,3株前列腺癌细胞的总ERK1/2无明显差异。在血清饥饿的状态下,LNCaP细胞无ERK1/2的活化,而PC-3和DU145细胞ERK1/2处于持续活化的状态。PD98059能够阻断EGF对3株前列腺癌细胞ERK1/2的激活。结论:MAPK通路的持续活化在前列腺癌的恶性进展中起重要作用,阻断此通路可以抑制前列腺癌细胞的增殖。

Objective： To investigate the change of mitogen activated protein kinase（MAPK） signaling pathway during prostate cancer progression, and therefore to explore its role on cell proliferation. Methods： MTT assay was used to examine the effects of epidermal growth factor （EGF） and PD98059 on proliferation of prostate cancer cell lines LNCaP, PC-3 and DU145, and western blotting to detect the level of total extracellular signal-regulated kinase 1/2 （ERK1/2）, the level of phospho-ERK1/2 before and after the EGF stimulation and PD98059 inhibition. Resuits： EGF promoted the prostate cancer cell growth, whereas PD98059 inhibited the cell growth and stopped the EGF from stimulating the LNCaP, PC-3 and DU145 cells. The total ERK1/2 level was not signiticantly different in the three cell lines, whereas the phospho-ERK1/2 was not detected with western blotting in LNCaP cell line and ERK1/2 activity was found in PC-3 and DU145. Conclusion： The MAPK transpass activity is promoted during the prostate cancer progression, suggesting that blocking the MAPK tmnspass can be used as a method for prostate cancer therapy.