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Apatinib-induced protective autophagy and apoptosis through the AKT-mTOR pathway in anaplastic thyroid cancer

Haoran Feng1,2, Xi Cheng1,2, Jie Kuang1,2

  • 1Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 200025, Shanghai, China.

Cell Death & Disease
|October 11, 2018
PubMed

Insights

Apatinib triggers both autophagy and apoptosis in anaplastic thyroid carcinoma (ATC) by impacting the AKT/mTOR pathway. Combining apatinib with autophagy inhibitors enhances tumor suppression, offering a promising new treatment strategy for ATC patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cellular Biology

Background:

  • Apatinib, a VEGFR-2 inhibitor, shows anti-cancer effects in various malignancies.
  • Previous research indicated apatinib induces apoptosis in anaplastic thyroid carcinoma (ATC).
  • The precise mechanism of apatinib's tumor-lethal action in ATC remains unclear.

Purpose of the Study:

  • To elucidate the direct functional mechanism of apatinib-induced tumor lethality in human ATC cells.
  • To investigate the roles of autophagy and the AKT/mTOR pathway in apatinib's anti-cancer effects on ATC.

Main Methods:

  • Investigated apatinib's effects on autophagy and apoptosis in human ATC cells.
  • Analyzed the involvement of the AKT/mTOR pathway, including p-AKT and p-mTOR signaling.
  • Evaluated the impact of inhibiting apatinib-induced autophagy on apoptosis and tumor suppression in vitro and in vivo, using chloroquine as an autophagy inhibitor.

Main Results:

  • Apatinib induced both autophagy and apoptosis in human ATC cells.
  • This induction was mediated by the downregulation of p-AKT and p-mTOR via the AKT/mTOR pathway.
  • Inhibiting autophagy enhanced apatinib-induced apoptosis, and the combination of apatinib with chloroquine significantly improved tumor suppression.

Conclusions:

  • Autophagy and AKT/mTOR signaling are crucial in apatinib-mediated ATC cell death.
  • Targeted molecular therapy combining apatinib with autophagy inhibitors presents a promising strategy for improving ATC treatment.
  • Anaplastic thyroid carcinoma patients may benefit from apatinib as a novel anti-cancer therapeutic agent.

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