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1066 SYSTEMIC TRANSDUCTION OF P16 INK4A ANTI-TUMOR PEPTIDE INHIBITS GROWTH OF MBT-2 BLADDER TUMOR CELL LINE GRAFT IN MICE

2011; Lippincott Williams & Wilkins; Volume: 185; Issue: 4S Linguagem: Inglês

10.1016/j.juro.2011.02.1103

1527-3792

Toru Shimazui, Kazuhiro Yoshikawa, Takahiro Kojima, Jun–ichi Miyazaki, Hiromu Inai, Hirotsugu Uemura, Eisaku Kondo,

Cancer Immunotherapy and Biomarkers

You have accessJournal of UrologyBladder Cancer: Basic Research1 Apr 20111066 SYSTEMIC TRANSDUCTION OF P16INK4A ANTI-TUMOR PEPTIDE INHIBITS GROWTH OF MBT-2 BLADDER TUMOR CELL LINE GRAFT IN MICE Toru Shimazui, Kazuhiro Yoshikawa, Takahiro Kojima, Jun Miyazaki, Hiromu Inai, Hirotsugu Uemura, and Eisaku Kondo Toru ShimazuiToru Shimazui Tsukuba, Japan , Kazuhiro YoshikawaKazuhiro Yoshikawa Nagakute, Japan , Takahiro KojimaTakahiro Kojima Hitachi, Japan , Jun MiyazakiJun Miyazaki Tsukuba, Japan , Hiromu InaiHiromu Inai Nasushiobara, Japan , Hirotsugu UemuraHirotsugu Uemura Higashiosaka, Japan , and Eisaku KondoEisaku Kondo Nagoya, Japan View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.1103AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES P16INK4A (p16), which is a key molecule of bladder tumor (BT) development, inhibits the activities of CDKs and then maintains the retinoblastoma protein (Rb) in its active hypophosphorylated state. In clinical samples, it is reported that abnormal p16 was observed in 50 to 70% of human BT. It is reported that p16 antitumor peptide dramatically inhibited growth of highly aggressive leukemia/lymphomas through restoration of p16 function using Wr-T peptide transporter system (Kondo E, Mol Cancer Ther 2004). In this study, we developed a systemic therapy of mouse-p16 peptide (m-p16) on subcutaneous p16-absent mouse BT. METHODS In vitro anti-tumor effect by p16 peptide was analyzed in 10 human BT cell lines using WST assay. The p16-absent MBT-2 cell line with 106 cells was s.c. injected to total of 50 KSN/SKC nude mice. Systemic peptide delivery to solid MBT-2 tumor was done by cardiac injection as follows: (A) PBS alone (control, n=10), (B) Wr-T alone (n=10), (C) 20 nM m-p16 alone, (D) 20 nM m-p16+Wr-T (n=10), or (E) 3 times of group D (n=10), was injected into the heart when the tumor had grown to 3 mm diameter. RESULTS Growth of p16-absent BT cell lines and thier hyperphosphorylation of Rbs were inhibited by p16 transduction in concentration dependent manner. Tumor growth was significantly inhibited by m-p16 in groups D (p=0.011) and E (p=0.00034) as compared with group A (Figure). Histological examination revealed that apoptosis by TUNEL staining of group E was increased and its Rb phosphorylation was inhibited as compared with group A (43% vs 23% and 27% vs 50%, respectively). CONCLUSIONS Systemic peptide delivery with p16 could restore the hypophosphorylation state of Rb and might be a useful tool for treatment of BT. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e428-e429 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Toru Shimazui Tsukuba, Japan More articles by this author Kazuhiro Yoshikawa Nagakute, Japan More articles by this author Takahiro Kojima Hitachi, Japan More articles by this author Jun Miyazaki Tsukuba, Japan More articles by this author Hiromu Inai Nasushiobara, Japan More articles by this author Hirotsugu Uemura Higashiosaka, Japan More articles by this author Eisaku Kondo Nagoya, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...