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Inhibition of signal transducer and activator of transcription 3 expression by RNA interference suppresses invasion through inducing anoikis in human colon cancer cells

查看全文 作  者:Yu [1]Fan;You-Li [1]Zhang;Ying [1]Wu;Wei [1]Zhang;Yin-Huan [1]Wang;Zhao-Ming [1]Cheng;Hua [2]Li 高影响力作者 机构地区:[1]Department of Gastroenterology, Affiliated Hospital, Jiangsu University, Zhenjiang 212001, Jiangsu Province,China;[2]Department of Pharmacology and Toxicology, DartmouthMedical School, Dartmouth Medical School, Har~over, NH 03755,United States高影响力机构 出  处:《World Journal of Gastroenterology》索引2008年第14卷第3期,共7页高影响力期刊 基  金:the Program of Science and Technology, Zhenjiang City, No. SH2006019 摘  要:AIM:To investigate the roles and mechanism of signal transducer and activator of transcription 3 (STAT3) in invasion of human colon cancer cells by RNA interference. METHODS: Small interfering RNA (siRNA) targeting Signal transducer and activator of transcription 3 (STAT3) was transfected into HT29 colon cancer cells. STAT3 protein level and DNA-binding activity of STAT3 was evaluated by western blotting and electrophoretic mobility shift assay (EMSA), respectively. We studied the anchorage-independent growth using colony formation in soft agar, and invasion using the boyden chamber model, anoikis using DNA fragmentation assay and terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL), respectively. Western blot assay was used to observe the protein expression of Bcl-xL and survivin in colon cancer HT29 cells. RESULTS: RNA interference (RNAi) mediated by siRNA leads to suppression of STAT3 expression in colon cancer cell lines. Suppression of STAT3 expression by siRNA could inhibit anchorage-independent growth, and invasion ability, and induces anoikis in the colon cancer cell line HT29. It has been shown that knockdown of STAT3 expression by siRNA results in a reduction in expression of Bcl-xL and survivin in HT29 cells. CONCLUSION: These results suggest that STAT3 siRNA can inhibit the invasion ability of colon cancer cells through inducing anoikis, which antiapoptotic genes survivin and Bcl-xL contribute to regulation of anoikis.These studies indicate STAT3 siRNA could be a useful therapeutic tool for the treatment of colon cancer. 关 键 词:结肠癌 RNA 症状 癌细胞
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