MEK1 和 MEK2 对人胰岛素和甘精胰岛素诱导的人膀胱癌 T24 细胞增殖的调节作用具有差异性。

MEK1 and MEK2 differentially regulate human insulin- and insulin glargine-induced human bladder cancer T24 cell proliferation.

机构信息

Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510120, China.

出版信息

Chin Med J (Engl). 2012 Dec;125(23):4197-201.

PMID:23217386

Abstract

BACKGROUND

Increased risk of bladder cancer has been reported in diabetic patients. This study was to investigate the roles of mitogen-activated protein kinase kinase (MEK) 1 and 2 in the regulation of human insulin- and insulin glargine-induced proliferation of human bladder cancer T24 cells.

METHODS

In the absence or presence of a selective inhibitor for MEK1 (PD98059) or a specific siRNA for MEK2 (siMEK2), with or without addition of insulin or glargine, T24 cell proliferation was evaluated by cell counting kit (CCK)-8 assay. Protein expression of MEK2, phosphorylation of ERK1/2 and Akt was analyzed by Western blotting.

RESULTS

T24 cell proliferation was promoted by PD98059 at 5 - 20 µmol/L, inhibited by siMEK2 at 25 - 100 nmol/L. PD98059 and siMEK2 remarkably reduced phosphorylated ERK1/2. Insulin- and glargine-induced T24 cell proliferation was enhanced by PD98059, suppressed while not blocked by siMEK2. Insulin- and glargine-induced ERK1/2 activation was blocked by PD98059 or siMEK2 treatment, whereas activation of Akt was not affected.

CONCLUSION

MEK1 inhibits while MEK2 contributes to normal and human insulin- and insulin glargine-induced human bladder cancer T24 cell proliferation.

摘要

背景

糖尿病患者膀胱癌风险增加。本研究旨在探讨丝裂原活化蛋白激酶激酶（MEK）1 和 2 在调节人胰岛素和甘精胰岛素诱导人膀胱癌 T24 细胞增殖中的作用。

方法

在不存在或存在 MEK1（PD98059）选择性抑制剂或 MEK2 特异性 siRNA（siMEK2）的情况下，加入或不加入胰岛素或甘精胰岛素，通过细胞计数试剂盒（CCK）-8 测定 T24 细胞增殖。通过 Western blot 分析 MEK2、ERK1/2 和 Akt 的磷酸化蛋白表达。

结果

PD98059 在 5-20 μmol/L 促进 T24 细胞增殖，siMEK2 在 25-100 nmol/L 抑制 T24 细胞增殖。PD98059 和 siMEK2 显著降低磷酸化 ERK1/2。PD98059 增强胰岛素和甘精胰岛素诱导的 T24 细胞增殖，而 siMEK2 抑制但不阻断该作用。PD98059 或 siMEK2 处理阻断胰岛素和甘精胰岛素诱导的 ERK1/2 激活，但不影响 Akt 激活。