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Gastrodin destabilizes survivin and overcomes pemetrexed resistance

Jinzhuang Liao1, Xiang Qing2, Gaoyan Deng3

  • 1Department of Radiology, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China; Cell Transplantation and Gene Therapy Institute, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China.

Cellular Signalling
|August 16, 2023
PubMed

Insights

Gastrodin, a natural compound, effectively inhibits non-small cell lung cancer (NSCLC) growth by reducing survivin levels. It also enhances apoptosis and overcomes resistance to chemotherapy, showing potential as an antitumor agent.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Survivin is a key protein in cancer development.
  • Non-small cell lung cancer (NSCLC) remains a significant health challenge.
  • Targeting survivin offers a potential therapeutic strategy for NSCLC.

Purpose of the Study:

  • To investigate the antitumor effects of gastrodin on NSCLC.
  • To elucidate the molecular mechanisms underlying gastrodin's action.
  • To evaluate gastrodin's potential in overcoming chemotherapy resistance.

Main Methods:

  • Cell viability and colony formation assays in NSCLC cell lines.
  • Western blotting to assess protein levels and signaling pathways.
  • In vivo xenograft tumor models and in vitro drug resistance studies.

Main Results:

  • Gastrodin suppressed NSCLC cell viability and colony formation dose-dependently.
  • Gastrodin induced apoptosis by activating the mitochondrial pathway and enhancing cleaved-caspase 3.
  • Gastrodin inhibited Akt/WEE1/CDK1 signaling, leading to survivin dephosphorylation and destabilization.
  • Gastrodin reduced NSCLC tumor growth in vivo and overcame pemetrexed resistance.

Conclusions:

  • Gastrodin exhibits significant antitumor activity against NSCLC.
  • Gastrodin's mechanism involves survivin downregulation via dephosphorylation and destabilization.
  • Gastrodin demonstrates potential as a therapeutic agent for NSCLC, including overcoming drug resistance.
Keywords:
GastrodinNon-small cell lung cancerPemetrexedSurvivinUSP19

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