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Silencing survivin activates autophagy as an alternative survival pathway in HCC cells

Yu-Jia Chang1, Li-Tzu Li, Hsin-An Chen

  • 1Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.

Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine
|July 11, 2014
PubMed

Insights

Suppressing survivin in liver cancer cells activates autophagy, a survival pathway. This suggests autophagy could be a therapeutic target for hepatocellular carcinoma (HCC) when survivin is inhibited.

Area of Science:

  • Oncology
  • Cell Biology
  • Molecular Biology

Background:

  • Autophagy is a cellular survival mechanism activated by nutrient deprivation.
  • Aberrant autophagy and its link to cancer progression are increasingly recognized.
  • Survivin, an anti-apoptotic molecule, is implicated in cancer therapeutic responses.

Purpose of the Study:

  • To investigate the role of autophagy in hepatocellular carcinoma (HCC) following survivin suppression.
  • To determine if autophagy acts as an alternative survival pathway in HCC cells with reduced survivin.

Main Methods:

  • Survivin knockdown (survivin-KD) was induced in HCC cells using siRNA.
  • Cell viability was assessed using MTT assay.
  • Autophagy markers, including stress granules, acridine orange staining, flow cytometry (SSC), and electron microscopy (autophagosomes), were analyzed.
  • Autophagy inhibition was achieved using 3-MA.

Main Results:

  • Survivin-KD cells showed a 20% reduction in survival.
  • Increased stress granules, acridine orange staining, and SSC shift were observed in survivin-KD cells.
  • Electron microscopy revealed a higher number of autophagosomes in survivin-KD cells.
  • Treatment with autophagy inhibitor 3-MA decreased cell survival in survivin-KD cells.

Conclusions:

  • Survivin suppression in HCC cells activates an autophagy signaling pathway.
  • Autophagy may serve as an alternative survival mechanism in HCC cells when survivin is inhibited.
  • These findings suggest potential new therapeutic strategies targeting autophagy in HCC.

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