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Bevacizumab Regulates Cancer Cell Migration by Activation of STAT3

Huan-Huan Wu1, Shuai Zhang, Huan Bian

  • 1Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing, China E-mail : kqwangyx@sina.com; guodazuo@sina.com.

Asian Pacific Journal of Cancer Prevention : APJCP
|October 6, 2015
PubMed

Insights

Bevacizumab differentially affects cancer cell migration, promoting it in some lines via the interleukin-6/signal transducer and activator of transcription 3 (IL-6/STAT3) pathway. Inhibitors blocked this bevacizumab-induced migration, revealing a key molecular mechanism.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Clinical observations suggest long-term bevacizumab use may enhance tumor invasiveness.
  • The molecular mechanisms underlying bevacizumab's effects on tumor cell behavior remain largely unelucidated.

Purpose of the Study:

  • To investigate the effects of bevacizumab on cancer cell migration and invasion.
  • To explore the role of the signal transducer and activator of transcription (STAT) 3 pathway in bevacizumab's action.
  • To identify potential molecular targets for modulating bevacizumab's effects.

Main Methods:

  • Exposure of four cancer cell lines (WSU-HN6, CAL27, Tca83, HeLa) to bevacizumab.
  • Assessment of cell migration and invasion.
  • Treatment with STAT3 inhibitors (niclosamide, S3I-201).
  • Analysis of interleukin-6 (IL-6) and phosphorylated (p)-STAT3 expression.

Main Results:

  • Bevacizumab promoted migration and invasion in WSU-HN6 and Tca83 cells.
  • Bevacizumab inhibited migration and invasion in CAL27 and HeLa cells.
  • STAT3 inhibitors blocked bevacizumab-induced migration in WSU-HN6 and Tca83 cells.
  • Bevacizumab upregulated IL-6 and p-STAT3 expression in a time-dependent manner.

Conclusions:

  • Bevacizumab exhibits differential effects on the migration of various cancer cell lines.
  • Bevacizumab-induced cancer cell migration is mediated through the IL-6/STAT3 signaling pathway.
  • Targeting the IL-6/STAT3 pathway may offer a strategy to counteract bevacizumab-induced tumor cell migration.

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