Fol. Biol. 2011, 57, 87-95
Unfolded Protein Response Suppresses Cisplatin-Induced Apoptosis via Autophagy Regulation in Human Hepatocellular Carcinoma Cells
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.
Keywords
unfolded protein response, Hsp27, autophagy, cisplatin, HCC cells.
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
Copyright
This is an open-access article distributed under the terms of the Creative Commons Attribution License.
