cc-122 and Disease-Models--Animal

Although gemcitabine-based chemotherapy is most recommended for pancreatic ductal adenocarcinoma (PDAC), its effectiveness is limited because of drug resistance. Given thalidomide's anti-tumor effects in solid tumors, we investigated the effect of avadomide, a novel thalidomide analog, on PDAC and explored its anti-tumor mechanisms.. PDAC cell lines, including gemcitabine-resistant (GR) clones derived from MiaPaCa2 cells, were used to evaluate the effects of avadomide. An annexin V assay, a cell cycle assay, and western blot analysis were performed to explain the mechanism of avadomide as an anti-tumor reagent. Moreover, we investigated the anti-tumor effect on tumor growth using a subcutaneous xenograft murine model.. Avadomide showed anti-tumor effects in human PDAC cell lines. The proportion of apoptotic cells and G0/G1 phase cells after avadomide treatment increased, especially in the GR PDAC clones. Western blot analysis also showed the induction of the apoptotic pathway by inhibiting the NF-κB process and G1 phase cell cycle arrest. The xenograft murine model revealed that the proportion of viable cells in the avadomide-treated group was lower than that in the untreated group.. Our findings suggest that avadomide could be a novel therapeutic option to overcome gemcitabine resistance in patients with PDAC.

Topics: Animals; Apoptosis; Carcinoma, Pancreatic Ductal; Cell Line, Tumor; Cell Proliferation; Deoxycytidine; Disease Models, Animal; Drug Resistance, Neoplasm; Gemcitabine; Humans; Mice; Pancreatic Neoplasms; Thalidomide; Xenograft Model Antitumor Assays