Tumor Biology

, Volume 35, Issue 10, pp 9957–9966 | Cite as

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

  • Yu-Jia Chang
  • Li-Tzu Li
  • Hsin-An Chen
  • Chin-Sheng Hung
  • Po-Li Wei
Research Article


Autophagy is a survival mechanism that is activated in response to nutrient deprivation. The link between aberrant autophagy and cancer has been increasingly recognized. Survivin, an anti-apoptotic molecule, and the autophagy pathway are correlated with therapeutic responses to cancer. However, the role of autophagy in cancer progression remains unclear. Here, we generated survivin knockdown cells (survivin-KD) by introducing a short interfering RNA (siRNA) into hepatocellular carcinoma (HCC) cells, and we observed a 20 % reduction in the survival of these survivin-KD cells, as determined by MTT assay. In addition, an increased number of stress granules, increased positive staining by acridine orange and a shift in the high side scatter (SSC) cell population in flow cytometry analysis were observed in survivin-KD cells. Furthermore, electron microscopy revealed an increased number of autophagosomes in survivin-KD cells compared with scrambled control cells. Finally, we treated cells with an autophagy inhibitor, 3-MA, and observed a decrease in cell survival in survivin-KD cells compared with scrambled control cells. Our study suggests that an autophagy signal may be activated after the anti-apoptotic molecule survivin is suppressed. This finding implies that autophagy may be an alternative survival pathway in HCC cells and may provide a basis for the development of new therapeutic strategies for HCC.


Survivin Autophagy HCC Anti-proliferation 



Hepatocellular carcinoma



This study was supported by grants from Taipei Medical University and Shuang Ho Hospital (101TMU-SHH-9) and Ministry of Science and Technology (NSC-101-2314-B-038-016-MY3 and NSC-101-2314-B-038-029-MY3).

Conflicts of interest



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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Yu-Jia Chang
    • 1
    • 2
    • 3
    • 4
    • 5
  • Li-Tzu Li
    • 6
  • Hsin-An Chen
    • 7
  • Chin-Sheng Hung
    • 2
    • 3
    • 4
    • 5
  • Po-Li Wei
    • 2
    • 3
    • 4
    • 5
    • 8
  1. 1.Graduate Institute of Clinical Medicine, College of MedicineTaipei Medical UniversityTaipeiTaiwan
  2. 2.Department of Surgery, School of Medicine, College of MedicineTaipei Medical UniversityTaipeiTaiwan
  3. 3.Division of General Surgery, Department of Surgery, Taipei Medical University HospitalTaipei Medical UniversityTaipeiTaiwan
  4. 4.Cancer Center, Taipei Medical University HospitalTaipei Medical UniversityTaipeiTaiwan
  5. 5.Taipei Medical UniversityTaipeiTaiwan
  6. 6.Institute of Stem Cell and Translational Cancer ResearchChang Gung Memorial HospitalLinkouTaiwan
  7. 7.Division of General Surgery, Department of Surgery, Shuang Ho HospitalTaipei Medical UniversityTaipeiTaiwan
  8. 8.Taipei CityTaiwan

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