Unfolded protein response suppresses cisplatin-induced apoptosis via autophagy regulation in human hepatocellular carcinoma cells

Folia Biol (Praha). 2011;57(3):87-95.


It has been shown that drug resistance is extremely common in hepatocellular carcinoma (HCC) and is one of the major problems in HCC chemotherapy. However, the detailed mechanisms remain largely unknown. We have previously shown that endoplasmic reticulum (ER) stress is involved in the tumorigenesis of HCC. Here, we demonstrated that the unfolded protein response (UPR) inhibits cisplatin-induced HCC cell apoptosis. In HCC cells, cisplatin treatment triggers the UPR, which subsequently inhibits cisplatin-induced apoptosis. Importantly, mild ER stress precondition suppresses the sensitivity of HCC cells to cisplatin-induced apoptosis through autophagy regulation. Furthermore, heat-shock protein 27 (Hsp27) is involved in the cytoprotective role of the UPR in cisplatin-induced apoptosis. We also demonstrated that Hsp27 inhibits cisplatin- induced HCC cell death through autophagy activation. Taken together, our results indicate that the UPR inhibits cisplatin-induced apoptosis in HCC cells, at least in part, by Hsp27-mediated autophagy activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects*
  • Apoptosis / physiology
  • Autophagy / drug effects*
  • Autophagy / physiology*
  • Carcinoma, Hepatocellular / pathology*
  • Cell Line, Tumor
  • Cisplatin / metabolism
  • Cisplatin / pharmacology*
  • Dithiothreitol / pharmacology
  • Endoplasmic Reticulum / drug effects
  • Endoplasmic Reticulum / physiology
  • HSP27 Heat-Shock Proteins / genetics
  • HSP27 Heat-Shock Proteins / metabolism
  • Heat-Shock Proteins
  • Heat-Shock Response
  • Humans
  • Liver Neoplasms / pathology
  • Molecular Chaperones
  • Tunicamycin / pharmacology
  • Unfolded Protein Response / physiology*


  • Antineoplastic Agents
  • HSP27 Heat-Shock Proteins
  • HSPB1 protein, human
  • Heat-Shock Proteins
  • Molecular Chaperones
  • Tunicamycin
  • Cisplatin
  • Dithiothreitol