MP50-06 SIMVASTATIN INHIBITS THE PROLIFERATION, MIGRATION AND INVASION OF ANDROGEN INDEPENDENT HUMAN PROSTATE CANCER CELLS VIA UP-REGULATION OF ANNEXIN A10

Abstract

You have accessJournal of UrologyProstate Cancer: Advanced (including Drug Therapy) II1 Apr 2016MP50-06 SIMVASTATIN INHIBITS THE PROLIFERATION, MIGRATION AND INVASION OF ANDROGEN INDEPENDENT HUMAN PROSTATE CANCER CELLS VIA UP-REGULATION OF ANNEXIN A10 Yoshiyuki Miyazawa, Yoshitaka Sekine, Haruo Kato, Yosuke Furuya, Hidekazu Koike, and Kazuhiro Suzuki Yoshiyuki MiyazawaYoshiyuki Miyazawa More articles by this author , Yoshitaka SekineYoshitaka Sekine More articles by this author , Haruo KatoHaruo Kato More articles by this author , Yosuke FuruyaYosuke Furuya More articles by this author , Hidekazu KoikeHidekazu Koike More articles by this author , and Kazuhiro SuzukiKazuhiro Suzuki More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.440AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Recently, statins have been being studied for their proapoptic and antimetastatic effects. However, the exact mechanisms of their anticancer action are still unclear. By using microarray, we found that up-regulation of Annexin A10 (ANXA10) was observed in PC-3 after treatment of simvastatin. ANXA10 is reported to have antitumor effects. In this study, we evaluated the effects of simvastatin on ANXA10 signaling in androgen independent prostate cancer cells. METHODS PC-3, LNCaP-LA and DU145 human PC cell lines were usey. In Gunma university hospital, prostate tissues (BPH; n = 15, Gleason score 7; n = 15 and Gleason score 8 to 10; n = 15) were collected at the time of prostate biopsy. To evaluate the effect of simvastatin and/or ANXA10 on PC-3 cells, we used a nude mouse tumor xenograft model with administration of simvastatin 5mg/kg, 50mg/kg and saline (as control group) via intraperitoneal injections. RESULTS Simvastatin inhibited proliferation of PC-3, LNCaP-LA and DU145 cells. The expressions of ANXA10 were up-regulated by simvastatin in PC-3, LNCaP-LA and DU145. Transfection with ANXA10 inhibited PC-3 cell proliferation, migration and invasion. Knockdown of ANXA10 by siRNA increased proliferation of PC-3 cells. In a nude mouse xenograft model of PC-3 cells, simvastatin induced both reductions in tumor size and up-regulations of ANXA10 expression (Fig.1). In human prostate biopsy samples, ANXA10 mRNA expression was significantly lower in prostate cancer groups than BPH group (Fig.2). Next, we focused on S100 calcium binding protein A4 (S100A4), which is reported to be correlated with aggressiveness and worse prognosis for patients with different types of carcinoma. The expression of S100A4 was down-regulated by both simvastatin and overexpression of ANXA10. Moreover, knockdown of S100A4 by siRNA inhibited proliferation, migration and invasion of PC-3 cells. CONCLUSIONS Our results suggest statins inhibit proliferation, migration and invasion of androgen independent prostate cancer cells by up-regulation of ANXA10. In addition, S100A4 plays an important role in the effects. It seems that statins may be beneficial in preventative and/or therapeutic treatment of prostate cancer. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e674 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Yoshiyuki Miyazawa More articles by this author Yoshitaka Sekine More articles by this author Haruo Kato More articles by this author Yosuke Furuya More articles by this author Hidekazu Koike More articles by this author Kazuhiro Suzuki More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...