title: Bevacizumab Regulates Cancer Cell Migration by Activation of STAT3.
abstract: There are numerous clinical cases indicating that long-term use of bevacizumab may increase the invasiveness of tumors. However, to date, little is known about underlying molecular mechanisms. Therefore, the purpose of our study was to investigate effects of bevacizumab in four cancer cells lines (WSU-HN6, CAL27, Tca83, and HeLa). It was found to promote migration and invasion in the WSU-HN6 and Tca83 cases, while exerting inhibitory effects in CAL27 and HeLa cells. The signal transducer and activator of transcription (STAT) 3 inhibitors niclosamide and S3I-201 inhibited the STAT3 signal pathway, which is activated by bevacizumab. These inhibitors also substantially blocked bevacizumab-induced migration of WSU-HN6 and Tca83 cells. Bevacizumab upregulated interleukin (IL)-6 and phosphorylated (p)-STAT3 expression time-dependently. Therefore, we propose that bevacizumab has differential effects on the migration of different cancer cell lines and promotes migration via the IL-6/STAT3 signaling pathway.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing, China E-mail : kqwangyx@sina.com; guodazuo@sina.com.
authors.forename: Huan-Huan
authors.initials: HH
authors.lastname: Wu
authors.forename: Shuai
authors.initials: S
authors.lastname: Zhang
authors.forename: Huan
authors.initials: H
authors.lastname: Bian
authors.forename: Xiao-Xu
authors.initials: XX
authors.lastname: Li
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.forename: Yin-Fei
authors.initials: YF
authors.lastname: Pu
authors.forename: Yi-Xiang
authors.initials: YX
authors.lastname: Wang
authors.forename: Chuan-Bin
authors.initials: CB
authors.lastname: Guo
mesh_terms: D000636:Aminosalicylic Acids / Q000494:pharmacology; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D001557:Benzenesulfonates / Q000494:pharmacology; D000068258:Bevacizumab / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D009534:Niclosamide / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000636:Aminosalicylic Acids; D020533:Angiogenesis Inhibitors; D001557:Benzenesulfonates; D015850:Interleukin-6; C520337:NSC 74859; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D000068258:Bevacizumab; D009534:Niclosamide