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Increased Autophagy Levels Mediate Cisplatin Resistance in Cisplatin-Resistant Cells While Also Rendering Them

Guihua Duan1,2, Zhengji Song1, Min Qi3

  • 1Department of Gastroenterology, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming 650032, China.

Biomed Research International
|December 13, 2018
PubMed

Insights

Cisplatin-resistant cancer cells with high autophagy are vulnerable to glutamine deprivation, leading to cell death. Rapamycin treatment can suppress the growth of these resistant cells by enhancing autophagy.

Area of Science:

  • Oncology
  • Cell Biology
  • Cancer Research

Background:

  • Autophagy maintains energy homeostasis and is implicated in cancer drug resistance.
  • The impact of high autophagy levels on tumor cell growth remains unclear.
  • Cisplatin (ddp) resistance in cancer is a significant clinical challenge.

Purpose of the Study:

  • To investigate the effect of glutamine (Gln) deprivation on cisplatin-resistant cells.
  • To explore the role of autophagy in mediating ddp resistance and sensitivity to Gln deprivation.
  • To evaluate the therapeutic potential of targeting autophagy in ddp-resistant cancers.

Main Methods:

  • Comparison of cisplatin-sensitive and -resistant cells under glutamine-deficient conditions.
  • Assessment of cell cycle arrest, apoptosis, and autophagy levels.
  • Analysis of the AMPK/ULK1 autophagy signaling pathway.
  • In vivo studies using rapamycin treatment in ddp-resistant cells.

Main Results:

  • Cisplatin-resistant cells exhibited increased sensitivity to glutamine deprivation, showing G1 arrest and apoptosis.
  • Higher basal autophagy levels in ddp-resistant cells mediated resistance.
  • Glutamine deficiency induced apoptosis in ddp-resistant cells via enhanced AMPK/ULK1 activation.
  • Rapamycin treatment suppressed the growth of ddp-resistant cells in vivo.

Conclusions:

  • Increased autophagy in ddp-resistant cells renders them vulnerable to glutamine deprivation.
  • Targeting autophagy induction with rapamycin is a potential strategy to suppress ddp-resistant tumor growth.
  • This study provides novel insights into the metabolic vulnerabilities of drug-resistant cancers.

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