ARC is highly expressed in nasopharyngeal carcinoma and confers X-radiation and cisplatin resistance

Abstract

Apoptosis repressor with caspase recruitment domain (ARC), an inhibitor of apoptosis, is primarily expressed in terminally differentiated tissues. Recent studies have revealed that ARC is highly expressed in a variety of human cancer cell lines and epithelial-derived cancers, which suggests that ARC plays an important role in the process of carcinogenesis. However, whether ARC is involved in the development of nasopharyngeal carcinoma (NPC) and the various roles it plays in NPC remain unclear. In the present study, we examined the expression of ARC in NPC cell lines and NPC tissues and the relationship between its subcellular expression and clinicopathological grade; moreover, we explored the effect of this protein on radiation resistance and chemoresistance in NPC cells. We found that cytoplasmic ARC was expressed at high levels in NPC tissues, at moderate levels in severe atypical hyperplasia and at low levels in benign nasopharyngeal tissues. High expression of cytoplasmic and nuclear ARC was correlated with advanced local invasion. However, only a small amount of nuclear ARC was expressed in NPC in contrast to cytoplasmic ARC. We also found that attenuation of ARC expression by miRNA resulted in decreased X-radiation and cisplatin resistance in NPC CNE-2 cells. In contrast, overexpression of ARC resulted in increased X-radiation and cisplatin resistance in NPC 6-10B cells. Furthermore, we demonstrated that ARC appears to be critical for blocking the activation of casapse-8 and casapse-2 in NPC cells subjected to X-radiation or cisplatin. These results suggest that high expression of ARC plays an important role in the pathogenesis of NPC and leads to X-radiation and cisplatin resistance in NPC.