Pancreatic cancer resistance to chemotherapy: Resensitization strategies using resveratrol

Despite tremendous efforts to develop novel therapeutic methods involving chemotherapy and radiotherapy, resistance to chemotherapeutic agents remains a major obstacle in pancreatic cancer (PC). Thus, studies to determine the molecular mechanisms involved in multiple drug resistance are essential for resensitizing tumor cells to therapeutic drugs. Several mechanisms are involved in chemoresistance, including overexpression of signals responsible for cell survival, drug efflux pumps, rapid efficiency in DNA repair, the high toxicity of drugs, and downregulation of apoptotic activity. Phytochemicals including resveratrol (Res), curcumin, and genistein have emerged as potential adjuncts for sensitizing tumor cells to chemotherapeutic agents. For instance, Res can sensitize various tumor cells including prostate cancer, lung carcinoma, multiple myeloma, and PC by modulating multiple signaling pathways including signal transducer and activator of transcription 3, nuclear factor-κβ, drug efflux systems, and cell survival proteins involved in developing resistance. This review discusses these various mechanisms of resistance and explores how, with its unique properties, Res is a potential therapeutic agent for PC.