Statin-mediated reduction of osteopontin expression induces apoptosis and cell growth arrest in ovarian clear cell carcinoma.
Poor prognosis in ovarian clear cell carcinoma is associated with the expression of a defined set of proteins including osteopontin (OPN) and integrin. Statins, a family of 3-hydroxy-3-methylglutaryl CoA reductase inhibitors, are currently being investigated for the treatment and prevention of cancer. In this study, we investigated the effects of simvastatin on ovarian clear cell carcinoma (OCCC) cells in vitro and in vivo and elucidated the mechanism of drug action. Changes in OPN gene expression were determined by real-time RT-PCR, and an MTT assay was performed to determine effects on cell proliferation. Finally, a xenograft tumor model was constructed to evaluate the effects of simvastatin on cell proliferation and apoptosis in vivo. According to our experimental results, OPN is an important protein in OCCC. Simvastatin inhibited OCCC cell proliferation, and the inhibition rate was approximately 40% to 50% after treatment with 10 µM simvastatin for 48 h. In the xenograft studies, simvastatin treatment resulted in a significant growth inhibition. Furthermore, the mice treated with simvastatin survived significantly longer compared to the control groups. In conclusion, simvastatin has anticancer effects in vitro and in vivo. Further confirmation of the anticancer effects of statins in future studies will increase the scope for OCCC treatment.
Department of Obstetrics and Gynecology, Sapporo Medical University, Sapporo, Japan. mmatsuura@sapmed.ac.jp
Motoki
M
Matsuura
Takahiro
T
Suzuki
Miwa
M
Suzuki
Ryoichi
R
Tanaka
Eiki
E
Ito
Tsuyoshi
T
Saito
D018262:Adenocarcinoma, Clear Cell / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D020287:In Situ Nick-End Labeling; D051379:Mice; D053495:Osteopontin / Q000096:biosynthesis* / Q000187:drug effects; D010051:Ovarian Neoplasms / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019821:Simvastatin / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D053495:Osteopontin; D019821:Simvastatin