Abstract
When apoptosis is suppressed in a neoplastic state, necroptosis may enable an anticancer response. In the present study, the association between apoptosis and necroptosis was assessed in a partial hepatectomy (PH)/diethylnitrosamine (DEN) rat model of hepatocarcinogenesis. Isolated oval cells (OCs) were analysed at 24, 48 and 72 h and at the first and second week of incubation. Phenotypic studies, apoptosis and necroptosis detection and proliferative activity assays were also performed on the OCs. The OCs were isolated from non-neoplastic (PH) and neoplastic (PH/DEN) livers, which expressed receptor interacting protein (RIP) 1 and RIP3. Western blot analysis revealed that the RIP1 and RIP3 expression in the PH/DEN OCs started to increase at 72 h and continually increased to the end of cell culture. Compared with the PH OCs, the cells isolated from PH/DEN rats exhibited significantly less potential for apoptosis (P<0.05). There were a minimal number of apoptotic PH/DEN OCs (2.82±1.1%) at 72 h. In addition, the PH/DEN OCs demonstrated progressive proliferative activity during incubation, which was significantly increased compared with the PH OCs at ≥72 h. The present study revealed that PH/DEN OCs, which trigger hepatic cancer, have a high proliferative activity and suppress apoptosis. It was also observed that, based on the expression of RIP3 and RIP1, necroptosis may be maintained and may serve as an alternative pathway for programmed PH/DEN OC death.