TRPV channels activation induces cell death in Human Pancreatic Ductal Adenocarcinoma cell lines

Introduction Pancreatic Ductal Adenocarcinoma is one of the most aggressive and lethal malignancy. The main therapeutic strategy is surgical resection followed by adjuvant chemotherapy, but only 10-20-% of patients have a resectable form, while if it is metastatic is not applicable. So new therapeutic approaches are necessary. Several studies demonstrated the importance of Transient Receptor Potential Vanilloid (TRPV) channels in physiological and pathological processes such as cell proliferation, apoptosis, differentiation, suggesting that they could be potential anticancer targets. Herein, we evaluated the involvement of TRPV channels in Overall Survival (OS) and Recurrence Free Survival (RFS) in PDAC patients. Then, using two human PDAC cell lines, PANC-1 and MIAPaCa-2, it was evaluated the expression of TRPV1,TRPV2, TRPV3 and TRPV4 channels, and the anticancer activity of a TRPV ligand, alone and in combination with gemcitabine and paclitaxel, two chemotherapeutic drugs used in PDAC therapy. Material and Methods Firstly, using data from Pan-cancer database, OS and RFS associated to TRPV channels expression in PDAC patients were calculated. Then, TRPV channels gene and protein expression was evaluated in PANC-1 and MIAPaCa-2 using western blot analysis and RT-PCR. TRPV ligand anticancer effect was studied evaluating the cytotoxicity and cell death, alone and in combination with gemcitabine and paclitaxel. In addition, modulation of PDAC cell death pathways in TRPV stimulated cells was evaluated by RT-PCR profile array. Results and Discussions Database data showed a significant correlation between OS and RFS, and TRPV1, TRPV3 and TRPV4 expression. The expression profile of TRPV channels in PDAC cell lines was determined. Activation of TRPV channels induced cytotoxicity and apoptotic cell death. The combination of the TRPV ligand with chemotherapeutic drugs increased their efficacy. Moreover, TRPV activation leaded to a modulation of cell death pathways. Conclusion These preliminary data evidenced as TRPV channels could be potential targets for PDAC therapy. Moreover, the activation of these channels could be and adjuvant in PDAC chemotherapy.