Du Dong-Shu, Yang Xiao-Zhong, Wang Qiong, Dai Wei-Jie, Kuai Wen-Xia, Liu Ye-Liu, Chu Dechang, Tang Xiao-Jun
Laboratory of Neuropharmacology and Neurotoxicology, Shanghai Key Laboratory of Bio-Energy Crops, College of Life Science, Shanghai University, Shanghai 200444, P.R. China.
Department of Digestion, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu 223300, P.R. China.
Mol Med Rep. 2016 Jan;13(1):550-4. doi: 10.3892/mmr.2015.4523. Epub 2015 Nov 6.
Cell division cycle 42 (CDC42), which is a member of the Rho GTPase family, has been reported to regulate the metastasis of various human cancer cells; however, the role of CDC42 in gastric cancer (GC) remains unclear. The present study aimed to investigate the effects of CDC42 on the proliferation, migration and invasion of GC. Furthermore, the molecular mechanisms underlying the effects of CDC42 on GC were explored. The expression levels of CDC42 in the AGS and SGC7901 human GC cell lines were reduced by RNA interference. Knockdown of CDC42 significantly inhibited the proliferation of AGS and SGC7901 cells, and it was suggested that this inhibitory process may be due to cell cycle arrest at G1/S phase and downregulation of cyclin A, cyclin D1, cyclin E and proliferating cell nuclear antigen. Furthermore, knockdown of CDC42 markedly inhibited the migration and invasion of GC cells, and suppressed the expression of matrix metalloproteinase 9. These results indicated that CDC42 is a key regulator involved in regulating the proliferation, migration and invasion of GC, and it may be considered a potential therapeutic target in GC.
细胞分裂周期蛋白42(CDC42)是Rho GTPase家族的成员之一,据报道可调节多种人类癌细胞的转移;然而,CDC42在胃癌(GC)中的作用仍不清楚。本研究旨在探讨CDC42对GC细胞增殖、迁移和侵袭的影响。此外,还探索了CDC42影响GC的分子机制。通过RNA干扰降低了AGS和SGC7901人GC细胞系中CDC42的表达水平。敲低CDC42可显著抑制AGS和SGC7901细胞的增殖,提示这种抑制过程可能是由于细胞周期停滞在G1/S期以及细胞周期蛋白A、细胞周期蛋白D1、细胞周期蛋白E和增殖细胞核抗原的下调所致。此外,敲低CDC42可显著抑制GC细胞的迁移和侵袭,并抑制基质金属蛋白酶9的表达。这些结果表明,CDC42是参与调节GC细胞增殖、迁移和侵袭的关键调节因子,可能是GC潜在的治疗靶点。