143 HIGH-FAT DIET INCREASES RENAL CANCER GROWTH ACCOMPANIED BY LEPTIN INCREASE, AND SURVIVIN INHIBITION IS EFFECTIVE FOR SIMVASTATIN RESISTANT RENAL CANCER

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You have accessJournal of UrologyKidney Cancer: Basic Research I1 Apr 2012143 HIGH-FAT DIET INCREASES RENAL CANCER GROWTH ACCOMPANIED BY LEPTIN INCREASE, AND SURVIVIN INHIBITION IS EFFECTIVE FOR SIMVASTATIN RESISTANT RENAL CANCER Hidekazu Koike, Takashi Nitta, Yoshitaka Sekine, Yosuke Furuya, Yasuyuki Morikawa, Hiroshi Matsui, Yasuhiro Shibata, and Kazuhiro Suzuki Hidekazu KoikeHidekazu Koike Maebashi, Japan More articles by this author , Takashi NittaTakashi Nitta Maeabshi, Japan More articles by this author , Yoshitaka SekineYoshitaka Sekine Maeabshi, Japan More articles by this author , Yosuke FuruyaYosuke Furuya Maeabshi, Japan More articles by this author , Yasuyuki MorikawaYasuyuki Morikawa Maeabshi, Japan More articles by this author , Hiroshi MatsuiHiroshi Matsui Maeabshi, Japan More articles by this author , Yasuhiro ShibataYasuhiro Shibata Maeabshi, Japan More articles by this author , and Kazuhiro SuzukiKazuhiro Suzuki Maeabshi, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.193AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Recently, there is a report that obesity is associated with a higher risk of clear-cell renal cell carcinoma. Statins might reduce risk of renal cell carcinoma in humans. In this study, we examined the mechanism of tumor growth by high-fat diet. Next, we studied the antitumor mechanism of simvastatin. Furthermore, in statin resistant renal cancer cells, we examined the role of survivin (a member of the inhibitor of apoptosis protein) and the antitumor sensitization effect due to survivin inhibition in statin treatment. METHODS Mice transplanted s.c. with caki1 cells were injected intraperitoneally with 20mg/kg simvastatin every day under high-fat or normal diet. We examined tumor growth and Leptin density of blood. Next, we examined the anticancer mechanism of simvastatin associated with IGF-1r on Caki1 cells. Furthermore, we examined the antitumor sensitization effect due to survivin inhibition in statin treatment for statin resistant caki1 and KMRC1 cells. RESULTS Tumor volume tended to be higher in the high-fat diet group than in the normal diet group. Leptin were increased in the high-fat diet group. Adiponectin tended to decrease in the high-fat diet group. Leptin increased cell proliferation. However, simvastatin did not decrease Leptin. In Caki1 cells, simvastatin inhibited cell proliferation decreasing gene expression levels of IGF-1r. Although simvastatin inhibited tumor growth, survivin mRNA were increased compared with control group. In simvastatin resistant caki1 cells, survivin gene expression levels were up-regulated, and simvastatin inhibited the cell proliferation in the presence of survivin siRNA. In KMRC1 cells, Low-dose simvastatin did not inhibit cell proliferation. However, in the presence of survivin siRNA, low-dose simvastatin inhibited KMRC1 cell proliferation. CONCLUSIONS High-fat diet increased renal cell tumor growth increasing Leptin and decreasing Adiponectin density of blood. Simvastatin has anticancer effect being associated with IGF-1r. Survivin is associated with simvastatin resistance of renal cancer cells. So, the down-regulation of survivin would be also a potential candidate for a novel approach to treat simvastatin resistant renal cancer. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e59-e60 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hidekazu Koike Maebashi, Japan More articles by this author Takashi Nitta Maeabshi, Japan More articles by this author Yoshitaka Sekine Maeabshi, Japan More articles by this author Yosuke Furuya Maeabshi, Japan More articles by this author Yasuyuki Morikawa Maeabshi, Japan More articles by this author Hiroshi Matsui Maeabshi, Japan More articles by this author Yasuhiro Shibata Maeabshi, Japan More articles by this author Kazuhiro Suzuki Maeabshi, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...