title: Inhibitory effect of atorvastatin on the cell growth of cardiac myxomas via the PTEN and PHLPP2 phosphatase signaling pathway.
abstract: Insulin-like growth factor 1 (IGF-1) is a molecule with strong proliferative effects, and statins have been reported to exhibit antitumor effects based on clinical and experimental studies. However, their effects on cardiac myxoma (CM) cells and the underlying signaling mechanism(s) are largely unknown. Therefore, we investigated whether the protein/lipid phosphatases and tensin homolog deleted on chromosome ten (PTEN) and pleckstrin homology domain leucine-rich repeat phosphatase 1 and 2 (PHLPP1 and 2) are involved in the proliferative effect of IGF-1 on CM cells and the pharmacological impact of atorvastatin. The activity of PTEN and PHLPPs was determined using specific substrate diC16PIP3 and pNPP. We found that IGF-1 enhanced CM cell proliferation and inhibited both PTEN and PHLPP2 activity in a concentration- and time-dependent manner. Atorvastatin acted counter to IGF-1 and reversed the above effects mediated by IGF-1. Both IGF-1 and atorvastatin did not affect the activity of PHLPP1 and the protein expression of the three phosphatases. The results suggest that IGF-1 may exert its proliferative effects by negatively regulating the PTEN/PHLPP2 signaling pathway in CM cells, and atorvastatin may be a potential drug for the treatment of CM by enhancing the activity of PTEN and PHLPP2.
authors.affiliation: Institute of Geriatric Cardiology, Chinese PLA General Hospital, Beijing, PR China. wxl301@yahoo.com
authors.forename: Xing-Li
authors.initials: XL
authors.lastname: Wu
authors.forename: Ding-You
authors.initials: DY
authors.lastname: Yang
authors.forename: Duan-Jun
authors.initials: DJ
authors.lastname: Tan
authors.forename: Heng-Chen
authors.initials: HC
authors.lastname: Yao
authors.forename: Wenhui
authors.initials: W
authors.lastname: Chai
authors.forename: Li
authors.initials: L
authors.lastname: Peng
mesh_terms: D000069059:Atorvastatin; D049109:Cell Proliferation / Q000187:drug effects; D006338:Heart Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D008875:Middle Aged; D009232:Myxoma / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism*; D011758:Pyrroles / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D006538:Heptanoic Acids; D011758:Pyrroles; D007334:Insulin-Like Growth Factor I; D000069059:Atorvastatin; C541572:PHLPP2 protein, human; D010749:Phosphoprotein Phosphatases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human