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Arsenic Trioxide Inhibits Cell Growth and Invasion via Down-Regulation of Skp2 in Pancreatic Cancer Cells

  • Gao, Jian-Kun (Department of Basic Medical Sciences, Sichuan College of Traditional Chinese Medicine) ;
  • Wang, Li-Xia (Cyrus Tang Hematology Center and Collaborative Innovation Center of Hematology, Jiangsu Institute of Hematology, The First Affiliated Hospital, Soochow University) ;
  • Long, Bo (Infectious Diseases Department, Mianyang 404 Hospital) ;
  • Ye, Xian-Tao (Cyrus Tang Hematology Center and Collaborative Innovation Center of Hematology, Jiangsu Institute of Hematology, The First Affiliated Hospital, Soochow University) ;
  • Su, Jing-Na (Cyrus Tang Hematology Center and Collaborative Innovation Center of Hematology, Jiangsu Institute of Hematology, The First Affiliated Hospital, Soochow University) ;
  • Yin, Xu-Yuan (Cyrus Tang Hematology Center and Collaborative Innovation Center of Hematology, Jiangsu Institute of Hematology, The First Affiliated Hospital, Soochow University) ;
  • Zhou, Xiu-Xia (Cyrus Tang Hematology Center and Collaborative Innovation Center of Hematology, Jiangsu Institute of Hematology, The First Affiliated Hospital, Soochow University) ;
  • Wang, Zhi-Wei (Cyrus Tang Hematology Center and Collaborative Innovation Center of Hematology, Jiangsu Institute of Hematology, The First Affiliated Hospital, Soochow University)
  • Published : 2015.05.18

Abstract

Arsenic trioxide (ATO) has been found to exert anti-cancer activity in various human malignancies. However, the molecular mechanisms by which ATO inhibits tumorigenesis are not fully elucidated. In the current study, we explored the molecular basis of ATO-mediated tumor growth inhibition in pancreatic cancer cells. We used multiple approaches such as MTT assay, wound healing assay, Transwell invasion assay, annexin V-FITC, cell cycle analysis, RT-PCR and Western blotting to achieve our goal. We found that ATO treatment effectively caused cell growth inhibition, suppressed clonogenic potential and induced G2-M cell cycle arrest and apoptosis in pancreatic cancer cells. Moreover, we observed a significant down-regulation of Skp2 after treatment with ATO. Furthermore, we revealed that ATO regulated Skp2 downstream genes such as FOXO1 and p53. These findings demonstrate that inhibition of Skp2 could be a novel strategy for the treatment of pancreatic cancer by ATO.

Keywords

Arsenic trioxide;Skp2;cell growth;apoptosis;pancreatic cancer

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