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 invasivenessof tumors. However, to date, little is known about underlying molecular mechanisms. Therefore, the purposeof 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 exertinginhibitory effects in CAL27 and HeLa cells. The signal transducer and activator of transcription (STAT) 3inhibitors 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 linesand promotes migration via the IL-6/STAT3 signaling pathway.