Involvement and targeted intervention of benzo(a)pyrene-regulated apoptosis related proteome modification and muti-drug resistance in hepatocellular carcinoma

Abstract

Abstract During the development of hepatocellular carcinoma (HCC), the mutual adaptation and interaction of HCC cells and the microenvironment play an important role. Benzo(a)pyrene (B[a]P) is a common environmental pollutant, which can induce the initiation of various malignant tumors, including HCC. However, the effects of B[a]P exposure on progression of HCC and the potential mechanisms remains largely uninvestigated. Here we found that, after the long-term exposure of HCC cells to low dose of B[a]P, it activated glucose-regulated protein 75 (GRP75), which then induced a modification of apoptosis-related proteome. Among them, we identified the X-linked inhibitor of apoptosis protein (XIAP) as a key downstream factor. XIAP further blocked the caspase cascade activation and promoted the acquisition of the anti-apoptosis abilities, ultimately leading to multi-drug resistance (MDR) in HCC. Furthermore, the abovementioned effects were markedly attenuated when we inhibited GRP75 by using 3,4-dihydroxycinnamic acid (caffeic acid, CaA). Collectively, our present study revealed the effects of B[a]P exposure on the progression of HCC, and identified GRP75 was a meaningful factor involved in.