细胞外信号调节激酶在卵巢癌中的表达及临床意义

The Expression and Clinical Significance of ERK in Ovarian Cancer

目的:研究细胞外信号调节激酶(ERK)在卵巢上皮癌中的表达及ERK激酶MEK1(丝裂原活化蛋白激酶激酶1)抑制剂PD98059对人卵巢癌细胞生长的抑制作用。方法:采用westernblot技术和免疫组化方法,对50例上皮性卵巢癌组织中ERK1和ERK2蛋白的表达进行了研究,分别以不同浓度的PD98059作用于卵巢癌细胞不同时间,通过MTT比色法观察PD98059对细胞增殖的抑制作用;应用扫描、透射电镜、细胞DNA提取及电泳实验研究PD98059对卵巢癌细胞的诱导凋亡作用。结果:ERK1和ERK2在卵巢癌中有过度表达,与正常卵巢及卵巢良性肿瘤相比,其差异有显著性。Ⅲ～Ⅳ期表达高于Ⅰ～Ⅱ期,差异有显著性。PD98059使卵巢癌细胞增殖比明显下降,其下降程度随PD98059浓度增高和作用时间延长而增强;PD98059100μM作用72h即可诱导卵巢癌细胞呈现典型的凋亡特征。结论:ERK的过度表达在卵巢癌的发生发展中起重要作用,PD98059具有抑制卵巢癌细胞生长和诱导凋亡作用。

Objective： To study the expression of extracellular signal-regulated kinase （ERK） in epithelial ovarian cancer and the effect of ERK kinase MEK1 inhibitor PD98059 on growth of the human ovarian cancer cell. Methods： Immunohistochemical method and western blot were employed in this study to detect distribution and quantity analysis of ERK protein, MTT assay was used to determine the suppressive effect of different concentration of PD98059 on ovarian cancer cell for 12, 24, 48 and 72 h. The apoptosis of ovarian cancer cell induced by PD98059 was detected by scanning electron microscope, transmission electron microscope and DNA-ladder electrophoresis. Results： The expression of ERK was higher in cancer than in normal ovarian tissue and benign ovarian tumor （P〈0.01）. It was significantly higher for ovarian cancer in stage Ⅲ and Ⅳ- than in stage Ⅰ and Ⅱ （P〈0.05）. The PD98059 suppressed the proliferation of ovarian cancer cell in a dose and time-dependent manner. The apoptosis of ovarian cancer cell induced by PD98059 appeared when PD98059 was at 100μM for 72 h. Conclusion： The over-expression of ERK may play an important role in initiation and development of the epithelial ovarian cancer. PD98059 could suppress the proliferation and induce the apoptosis of ovarian caneer cell.