Fol. Biol. 2011, 57, 87-95

https://doi.org/10.14712/fb2011057030087

Unfolded Protein Response Suppresses Cisplatin-Induced Apoptosis via Autophagy Regulation in Human Hepatocellular Carcinoma Cells

R. Chen1, R. Y. Dai2, C. Y. Duan2, Y. P. Liu2, S. K. Chen3, D. M. Yan2, C. N. Chen2, M. Wei4, Hong Li2

1Department of Public Health, Luzhou Medical College, Luzhou, Sichuan, P.R. China
2Department of Biochemistry, Luzhou Medical College, Luzhou, Sichuan, P.R. China
3Department of Biology, Luzhou Medical College, Luzhou, Sichuan, P.R. China
4The Affiliated Hospital of Chinese Traditional Medicine, Luzhou Medical College, Luzhou, Sichuan, P.R. China

Received November 2010
Accepted January 2011

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.

Funding

Research was supported by the projects from National Natural Science Foundation of China (No. 81000886) and supported by the grants from Sichuan (Nos. 2009SZ0117 and 09ZA050).

References

36 live references