Mechanism of action of salinomycin on growth and migration in pancreatic cancer cell lines

Objectives: Pancreatic cancer is one of the most aggressive and lethal cancers worldwide and there are few effective treatments. Recently, salinomycin (Sal) was reported to alter proliferation and apoptosis in various tumors. This prompted us to investigate the effect of Sal on pancreatic cancer cells and to explore the possible molecular mechanism in vitro. Methods: After treatment with Sal, pancreatic cancer cell viability and apoptosis were analyzed by Hoechst 33342 staining and flow cytometry, respectively. Invasion and metastasis of pancreatic cancer cells were assayed by a Transwell migration assay. Flow cytometiy was also used to assessed the fraction of CD133(+) cell subpopulations. The expression of proliferating cell nuclear antigen (PCNA), Bcl-2, E-cadherin, and Wnt/beta-catenin signaling-related proteins were detected by RT-PCR and western blot. Results: Sal inhibited the growth and migration of pancreatic cancer cells in vitro in a dose- and time-dependent manner. We found that the proportion of CD133+ cell subpopulations decreased after treatment with Sal in pancreatic cancer cell lines at the same time. The percentage of apoptotic cells was increased after Sal treatment. Compared with control groups, Bax and E-cadherin were significantly upregulated, and Bcl-2 and PCNA were significantly downregulated in Sal-treated cells. The expression of Wnt/beta-catenin signaling-related proteins (beta-catenin and p-GSK-3 beta) was inhibited. Conclusions: These results indicate that Sal could influence the cell growth and migration in pancreatic cancer cells in vitro, which may occur by inhibition of Wnt/beta-catenin signaling. Copyright (C) 2012, IAP and EPC. Published by Elsevier India, a division of Reed Elsevier India Pvt. Ltd. All rights reserved.