HIV protease inhibitors sensitize human head and neck carcinoma cells to radiation by activating ER stress (762.2)

Abstract

Head and neck cancers are the eighth most common cancer worldwide. Despite significant advances in the delivery of treatment and surgical reconstruction, the mortality rates for this disease have not improved in the past 4 decades. Our previous study has shown that HIV protease inhibitors (HIV PIs) induce cell apoptosis via activating ER stress. It also has been reported that a few HIV PIs are able to radiosensitize tumor cells. However, the underlying cellular mechanisms remain to be identified. The aim of this study was to examine whether HIV PIs activate the ER stress response and sensitize human head and neck carcinoma cells to radiation. Methods: Human SQ20B and Fadu cells and the most commonly used HIV PIs, lopinavir and ritonavir, were used in this study. The mRNA and protein levels of ER stress‐related genes (CHOP, ATF4, XBP‐1, and GRP78) were detected by real time RT‐PCR and Western blot, respectively. Cell viability and apoptosis were analyzed using Cellometer Vision CBA. After treatment with HIV PIs, cells were irradiated at a dose of 2G or 4G. Colonies were stained and counted 10 days after irradiation. Results: HIV PIs significantly induced activation of ER stress and apoptosis. Treatment of HIV PIs inhibited Akt phosphorylation and increased tumor cell sensitivity to irradiation‐induced cell death. Conclusion: HIV PIs sensitize human head and neck carcinoma cells to radiation by activating ER stress.Grant Funding Source: NIH/NIDDK, China natiional science foundation