Wu Huan-Huan, Zhang Shuai, Bian Huan, Li Xiao-Xu, Wang Lin, Pu Yin-Fei, Wang Yi-Xiang, Guo Chuan-Bin
Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing, China E-mail :
Asian Pac J Cancer Prev. 2015;16(15):6501-6. doi: 10.7314/apjcp.2015.16.15.6501.
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.
有大量临床病例表明，长期使用贝伐单抗可能会增加肿瘤的侵袭性。然而，迄今为止，对其潜在分子机制知之甚少。因此，我们研究的目的是调查贝伐单抗对四种癌细胞系（WSU-HN6、CAL27、Tca83和HeLa）的影响。结果发现，它在WSU-HN6和Tca83细胞系中促进迁移和侵袭，而在CAL27和HeLa细胞中发挥抑制作用。信号转导子和转录激活子（STAT）3抑制剂氯硝柳胺和S3I-201抑制了由贝伐单抗激活的STAT3信号通路。这些抑制剂也显著阻断了贝伐单抗诱导的WSU-HN6和Tca83细胞的迁移。贝伐单抗可时间依赖性地上调白细胞介素（IL）-6和磷酸化（p）-STAT3的表达。因此，我们认为贝伐单抗对不同癌细胞系的迁移有不同影响，并通过IL-6/STAT3信号通路促进迁移。
