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

Hailei Du, Weiping Yang, Lin Chen, Baiyong Shen, Chenghong Peng, Hongwei Li, David K. Ann, Yun Yen, Wihua Qiu

Research output: Contribution to journalArticle

19 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2049-2057
Number of pages9
JournalInternational Journal of Oncology
Volume40
Issue number6
DOIs
Publication statusPublished - Jun 1 2012
Externally publishedYes

Keywords

  • Autophagy
  • Hepatocellular carcinoma
  • Hypoxia
  • Ischemia
  • Reperfusion

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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