结直肠癌中MEK2/ERK信号传导通路的研究

目的　研究丝裂原激活化蛋白激酶 (MAPK )中MEK2 /ERK信号传导通路在结直肠癌发生发展中的作用。方法　 ( 1)采用Westernblot检测 5 2例结直肠癌组织及其邻近肠黏膜中MEK 2蛋白的表达。 ( 2 )用丝裂原细胞外激酶 (MEK )抑制剂作用于结肠癌细胞系SW 480 ,然后以MTT法检测细胞增殖状态 ;用Westernblot检测MEK2 ,p ERK及其靶基因产物C myc的表达。结果　结直肠癌组织中MEK2蛋白表达水平明显高于邻近的肠黏膜 (P <0 .0 5 ) ,且与肿瘤的分化、Dukes分期及淋巴结转移有关 (P <0 .0 5 )。应用MEK的抑制剂后SW 480细胞中MEK2 ,p ERK ,C myc表达水平随作用时间延长而下降。结论　MEK2活性增高与结直肠癌细胞侵袭力有关 ,阻断MEK2 /ERK信号传导通路可以抑制结肠癌细胞的增殖 ,促进其凋亡。

Study of MEK2/ERK signal transduction pathway in the colorectal cancer

Objective To study the role of MEK2/ERK signal transduction pathway in the development of colorectal cancer. Methods (1)Western blot analysis was performed on cancerous tissues and adjacent colonic tissues in 45 patients with colorectal cancers.(2)Human colorectal cancer cell line SW480 was treated with MEK inhibitor,and then MTT assay was used to measure the SW480 cells proliferation;and the expression of MEK2, p-ERK and C-myc in SW480 cells were measured by western blot. Results MEK2 protein level was increased in colorectal cancer compared with adjacent mucosa (P<0.05). The overexpression of MEK2 in cancerous tissue was related to the Dukes stage, differentiation and lymph nodes metastasis (P<0.05). There were significant correlation between MEK2 expression and clinicopalhological parameters such as tumor size, serosa invasion and distant metastasis. SW480 treated with MEK inhibitor PD98059 resulted in significant growth inhibition and downregulation of MEK2, p-ERK and C-myc. Conclusions The increase of MEK2 may correlate with the invisive potention of colorectal cancer. Blocking MEK2/ERK signal transduction pathway could inhibit the growth of SW480 cells.