Nutlin-3 cooperates with doxorubicin to induce apoptosis of human hepatocellular carcinoma cells through p53 or p73 signaling pathways

摘要

Purpose Despite recent advances in chemotherapeutic agents for Hepatocellular carcinoma (HCC) treatment, the results of chemotherapy remain unsatisfactory. Doxorubicin (DOX) still represents the cornerstone in HCC chemotherapy, but resistance and toxicity to normal cells are major obstacles to successful chemotherapy. Therefore, new active agents in HCC chemotherapy and agents that increase the chemosensitivity of HCC cells to DOX are still urgently required. Nutlin-3 is a small-molecule inhibitor that acts to inhibit murine double minute-2 (MDM2) binding to p53 or p73, and subsequently activates p53- or p73-dependent apoptosis signaling pathway. This study was designed to investigate whether Nutlin-3 alters cell toxicity to HCC cells following DNA damage and to assess the suitability of DOX/Nutlin-3 as a chemotherapeutic combination in HCC chemotherapy.