title: Mechanism of action of salinomycin on growth and migration in pancreatic cancer cell lines.
abstract: OBJECTIVE
  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 cytometry 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/β-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/β-catenin signaling-related proteins (β-catenin and p-GSK-3β) 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/β-catenin signaling.
authors: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University of Medicine, Shanghai 200072, PR China.
authors: Lei
authors: L
authors: He
authors: Fan
authors: F
authors: Wang
authors: Wei-Qi
authors: WQ
authors: Dai
authors: Dong
authors: D
authors: Wu
authors: Chun-Lei
authors: CL
authors: Lin
authors: Shu-Mei
authors: SM
authors: Wu
authors: Ping
authors: P
authors: Cheng
authors: Yan
authors: Y
authors: Zhang
authors: Miao
authors: M
authors: Shen
authors: Chen-Feng
authors: CF
authors: Wang
authors: Jie
authors: J
authors: Lu
authors: Ying-Qun
authors: YQ
authors: Zhou
authors: Xuan-Fu
authors: XF
authors: Xu
authors: Ling
authors: L
authors: Xu
authors: Chuan-Yong
authors: CY
authors: Guo
mesh_terms: D000071916:AC133 Antigen; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D015703:Antigens, CD; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects*; D006023:Glycoproteins / Q000037:antagonists & inhibitors; D006801:Humans; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology; D010455:Peptides / Q000037:antagonists & inhibitors; D011714:Pyrans / Q000494:pharmacology*; D000095662:Polyether Polyketides
chemical_list: D000071916:AC133 Antigen; D000903:Antibiotics, Antineoplastic; D015703:Antigens, CD; D006023:Glycoproteins; D010455:Peptides; D011714:Pyrans; C000606023:PROM1 protein, human; C010327:salinomycin; D000095662:Polyether Polyketides