Chen Jing-Song, Liang Qing-Mo, Li Hua-Shu, Yang Jie, Wang Song, Long Jian-Wu
Department of Oncology, Affiliated Nanhua Hospital, University of South China, Hunan Province, PR China.
Pharmazie. 2009 Feb;64(2):126-31.
Somatostatin can suppress the growth of various tumor cells including colonic cancer. Activated Wnt/ beta-catenin signaling pathway plays a critical role in tumorgenesis and development of colorectal cancer. However, the effect of somatostatin on Wnt/beta-catenin signaling pathway remains unknown. Thus, we investigated the effect of octreotide on Wnt/beta-catenin signaling pathway in human colonic cancer cell SW480. The results of 3-(4,5-imethyl thiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) and flow cytometric assays showed that octreotide inhibited growth, induced apoptosis and arrested the G1 cell cycle of SW480 cells in a dose-dependent manner. We demonstrated that octreotide significally up-regulated and down-regulated 13 genes and 17 genes in Wnt/beta-catenin signaling using microarray, respectively. Furthermore, as evidenced by western blot, beta-catenin protein level decreased, whereas phosphorylated beta-catenin protein level increased under octreotide. The present study reveals that octreotide can inhibit human colonic cancer cell growth through inhibition of Wnt/beta-catenin signaling pathway.
生长抑素可抑制包括结肠癌细胞在内的多种肿瘤细胞的生长。激活的Wnt/β-连环蛋白信号通路在结直肠癌的发生和发展中起关键作用。然而,生长抑素对Wnt/β-连环蛋白信号通路的影响尚不清楚。因此,我们研究了奥曲肽对人结肠癌细胞SW480中Wnt/β-连环蛋白信号通路的影响。3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐(MTT)和流式细胞术检测结果显示,奥曲肽以剂量依赖的方式抑制SW480细胞的生长、诱导凋亡并使细胞周期停滞于G1期。我们通过基因芯片证明,奥曲肽分别显著上调和下调了Wnt/β-连环蛋白信号通路中的13个基因和17个基因。此外,蛋白质免疫印迹法表明,在奥曲肽作用下,β-连环蛋白蛋白水平降低,而磷酸化β-连环蛋白蛋白水平升高。本研究表明,奥曲肽可通过抑制Wnt/β-连环蛋白信号通路来抑制人结肠癌细胞的生长。