title: Arsenic Trioxide Inhibits Cell Growth and Invasion via Down- Regulation of Skp2 in Pancreatic Cancer Cells.
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.
authors.affiliation: Department of Basic Medical Sciences, Sichuan College of Traditional Chinese Medicine, Mianyang, Sichuan, China E-mail : zwang6@bidmc.harvard.edu, xxzhou@suda.edu.cn.
authors.forename: Jian-Kun
authors.initials: JK
authors.lastname: Gao
authors.forename: Li-Xia
authors.initials: LX
authors.lastname: Wang
authors.forename: Bo
authors.initials: B
authors.lastname: Long
authors.forename: Xian-Tao
authors.initials: XT
authors.lastname: Ye
authors.forename: Jing-Na
authors.initials: JN
authors.lastname: Su
authors.forename: Xu-Yuan
authors.initials: XY
authors.lastname: Yin
authors.forename: Xiu-Xia
authors.initials: XX
authors.lastname: Zhou
authors.forename: Zhi-Wei
authors.initials: ZW
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D010087:Oxides / Q000494:pharmacology*; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D044786:S-Phase Kinase-Associated Proteins / Q000378:metabolism*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D014945:Wound Healing / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D001152:Arsenicals; D010087:Oxides; D044786:S-Phase Kinase-Associated Proteins; D000077237:Arsenic Trioxide