Emerging role of autophagy during ischemia-hypoxia and reperfusion in hepatocellular carcinoma

  • Authors:
    • Hailei Du
    • Weiping Yang
    • Lin Chen
    • Baiyong Shen
    • Chenghong Peng
    • Hongwei Li
    • David K. Ann
    • Yun Yen
    • Weihua Qiu
  • View Affiliations

  • Published online on: March 26, 2012     https://doi.org/10.3892/ijo.2012.1415
  • Pages: 2049-2057
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Abstract

Hepatocellular carcinoma (HCC) is the most common primary malignancy found in the liver. Autophagy is the intracellular bulk degradation process for long-lived proteins and dysfunctional organelles. In this study, we report that autophagy plays a role in HCC cell proliferation in response to ischemia-hypoxia (I/H) and reperfusion and discuss its potential therapeutic implications. By establishing a simulated model in cultured HepG2 (p53 wild-type) and Hep3B (p53 null) hepatoma cells in vitro, we found that exposure to I/H induced a significant increase in microtubule-associated protein 1 light chain 3 (LC3) lipidation and subsequent LC3 puncta formation. While the proliferation of HCC cells was stimulated upon acute I/H exposure compared to that of control, inhibition of autophagy by autophagy-related protein 7 interference abolished it. In addition, the steady-state levels of sequestosome 1 (p62) in both HepG2 and Hep3B cells were reduced following I/H exposure, supporting the notion that acute I/H induces autophagy. Intriguingly, the p62 level further decreased during reperfusion following I/H, accompanied by increased LC3 lipidation. The intracellular reactive oxygen species (ROS) accumulated during acute I/H exposure and persisted through reperfusion in both HepG2 and Hep3B cells and the ROS levels increased at a much faster rate during reperfusion than during I/H periods in both cells. Autophagy functions as a promoter for HCC cell survival during acute I/H and reperfusion and this also points to potential therapy for hepatoma by perturbing the acute I/H-reperfusion-autophagy axis.

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June 2012
Volume 40 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Du H, Yang W, Chen L, Shen B, Peng C, Li H, Ann DK, Yen Y and Qiu W: Emerging role of autophagy during ischemia-hypoxia and reperfusion in hepatocellular carcinoma. Int J Oncol 40: 2049-2057, 2012
APA
Du, H., Yang, W., Chen, L., Shen, B., Peng, C., Li, H. ... Qiu, W. (2012). Emerging role of autophagy during ischemia-hypoxia and reperfusion in hepatocellular carcinoma. International Journal of Oncology, 40, 2049-2057. https://doi.org/10.3892/ijo.2012.1415
MLA
Du, H., Yang, W., Chen, L., Shen, B., Peng, C., Li, H., Ann, D. K., Yen, Y., Qiu, W."Emerging role of autophagy during ischemia-hypoxia and reperfusion in hepatocellular carcinoma". International Journal of Oncology 40.6 (2012): 2049-2057.
Chicago
Du, H., Yang, W., Chen, L., Shen, B., Peng, C., Li, H., Ann, D. K., Yen, Y., Qiu, W."Emerging role of autophagy during ischemia-hypoxia and reperfusion in hepatocellular carcinoma". International Journal of Oncology 40, no. 6 (2012): 2049-2057. https://doi.org/10.3892/ijo.2012.1415