Jianwei Zhou
Nanjing Medical University, China
Title: JWA gene based targeting peptide inhibits melanoma proliferation and metastasis
Biography
Biography: Jianwei Zhou
Abstract
Cancer metastasis is still the biggest challenge to cancer patients worldwide. Melanoma is the most malignant tumor due to its rapid metastatic capacity and shorter survival rate. The JWA gene, also known as ARL6IP5, is initially cloned from a retinoid acid induced cell differentiation cell culture model in HBE (human bronchial epithelial) cells. JWA is also identified as an multi-functional protein in both normal and cancer cells. In normal cells, JWA works as an active ROS (reactive oxygen species) response gene and DNA repair protein; however, in cancer cells, JWA exerts a tumor suppressor role to inhibit cell migration, proliferation, angiogenesis and chemoresistance in some cancers including melanoma and gastric cancer. Here, we have developed a JWA gene based polypeptide (PJP1-RGD) which is able to specifically target overexpressed integrin αvβ3 on membrane of melanoma cells by its RGD linker. Our data showed 50 mg.kg/day of PJP1-RGD could effectively inhibit xenograft tumor growth of both B16H10 and A375 melanoma cells in mice, suppressed its metastasis and improved mice survival. The anticancer effect of PJP1-RGD is comparable to 80 mg.kg/day Dacarbazine, a first line drug for clinical melanoma chemotherapy. More importantly, a synergistic role was observed between PJP1-RGD and Dacarbazine in the treatment of melanoma. The combined use of PJP1-RGD (50 mg.kg/day) and Dacarbazine (40 mg.kg/day) indicated an enhanced inhibitory effects but less side effects of Dacarbazine. In conclusion, PJP1-RGD targeting peptide might be an useful anti-cancer metastasis candidate and with translational significance in drug development.