159 PYRROLE IMIDAZOLE POLYAMIDE TARGETING MMP-9 INHIBITS INVASIVENESS OF RENAL CARCINOMA CELLS

Abstract

You have accessJournal of UrologyKidney Cancer: Basic Research (I)1 Apr 2013159 PYRROLE IMIDAZOLE POLYAMIDE TARGETING MMP-9 INHIBITS INVASIVENESS OF RENAL CARCINOMA CELLS Kenya Yamaguchi, Aya Sato, Daisuke Obinata, Tomohiro Igarashi, Katsuhiko Sato, Junichi Mochida, Nozomu Kawata, Satoru Takahashi, and Kyoko Fujiwara Kenya YamaguchiKenya Yamaguchi Tokyo, Japan More articles by this author , Aya SatoAya Sato Tokyo, Japan More articles by this author , Daisuke ObinataDaisuke Obinata Tokyo, Japan More articles by this author , Tomohiro IgarashiTomohiro Igarashi Tokyo, Japan More articles by this author , Katsuhiko SatoKatsuhiko Sato Tokyo, Japan More articles by this author , Junichi MochidaJunichi Mochida Tokyo, Japan More articles by this author , Nozomu KawataNozomu Kawata Tokyo, Japan More articles by this author , Satoru TakahashiSatoru Takahashi Tokyo, Japan More articles by this author , and Kyoko FujiwaraKyoko Fujiwara Tokyo, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.1539AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES We already reported association between poor prognosis and overexpression of matrix metalloproteinase (MMP) 9 of surgical specimen in clinical renal cell carcinoma. Pyrrole imidazole polyamide (PI polyamide) is a sequence-specific inhibitor of transcription and is composed of two aromatic aminoacids (N-methylpyrrole (Py) and N-methyl imidazole (Im)). It binds to the minor groove of the DNA double helix with the same affinity and specificity of usual DNA binding proteins. In this study, we investigated whether pyrrole imidazole polyamide (PIP) targeting MMP9 has an inhibitory effect for invasiveness of renal carcinoma cells. METHODS We developed two types of PI polyamide targeting MMP-9, which bounds for NF-kB binding site (NFkB-PI) or for AP-1 binding site (AP1-PI) (Figure 1). By using human renal cell carcinoma (RCC) cell line Caki-2, PI polyamides were applied at 3 micro-M and 10 micro-M in concentration. We evaluated expression of MMP-9 mRNA by RT-quantative PCR (RT-qPCR), cell proliferation by WST8 and cell invasion using Matrigel invasion assay. RESULTS For Caki-2 cells, 3 micro-M and 10 micro-M NFkB-PI significantly inhibited mRNA expression of MMP-9 (Figure 2). They also inhibited cell invasion with significance (Figure 3). Cell proliferation was not inhibited by NFkB-PI. On the other hand, no effect for the mRNA expression, cell proliferation or invasion was observed in AP1-PI. CONCLUSIONS We confirmed inhibitory effects of NFkB-PI for expression of MMP-9 and subsequent invasion in Caki-2 cells. Although it is necessary to confirm these effects in vivo in future, a possibility was suggested of NFkB-PI as a new therapeutic agent for renal cell carcinoma. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e65-e66 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kenya Yamaguchi Tokyo, Japan More articles by this author Aya Sato Tokyo, Japan More articles by this author Daisuke Obinata Tokyo, Japan More articles by this author Tomohiro Igarashi Tokyo, Japan More articles by this author Katsuhiko Sato Tokyo, Japan More articles by this author Junichi Mochida Tokyo, Japan More articles by this author Nozomu Kawata Tokyo, Japan More articles by this author Satoru Takahashi Tokyo, Japan More articles by this author Kyoko Fujiwara Tokyo, Japan More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...