MP49-14 SYSTEMIC TRANSDUCTION OF P16INK4A ANTITUMOR PEPTIDE INHIBITS LUNG METASTASIS OF MBT-2 BLADDER TUMOR CELL LINE IN MICE

Abstract

You have accessJournal of UrologyBladder Cancer: Basic Research III1 Apr 2015MP49-14 SYSTEMIC TRANSDUCTION OF P16INK4A ANTITUMOR PEPTIDE INHIBITS LUNG METASTASIS OF MBT-2 BLADDER TUMOR CELL LINE IN MICE Toru Shimazui, Kazuhiro Yoshikawa, Jun Miyazaki, Kazuhiko Uchida, Atsushi Yamauchi, Mikinobu Ohtani, and Hiroyuki Nishiyama Toru ShimazuiToru Shimazui More articles by this author , Kazuhiro YoshikawaKazuhiro Yoshikawa More articles by this author , Jun MiyazakiJun Miyazaki More articles by this author , Kazuhiko UchidaKazuhiko Uchida More articles by this author , Atsushi YamauchiAtsushi Yamauchi More articles by this author , Mikinobu OhtaniMikinobu Ohtani More articles by this author , and Hiroyuki NishiyamaHiroyuki Nishiyama More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.518AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES P16INK4a (p16) is a key molecule of bladder tumor (BT) development, and we have previously reported that p16 antitumor peptide inhibited growth of subcutaneous BT graft through restoration of p16 function using Wr-T peptide transporter system in mice (Int J Oncol, 2013;42:543). Here, we evaluate the efficacy and toxicity of mouse p16 peptide administration on mouse lung metastasis model for BT. METHODS Mouse lung metastases were developed by tail vein injection of p16-absent MBT-2 cell line. Six-week-old C3H/He female mice were divided into 3 groups as follows: control group (n=12), single treatment group (n=12) at 3rd experimental day and triple treatment group (n=10) at 3rd, 5th and 7th experimental day. Treatment was also performed by tail vein injection using mixture of 80nmol mouse p16 and 50nmol Wr-T. At 14th experimental day, the lung metastases were histologically evaluated. As for the toxicity evaluation of p16 peptide transduction, low or high dose treatment was performed in five of 5-week-old C3H/He mice for each dose and evaluated by blood analyses and histological findings at early or late experimental phase. RESULTS The lung metastases were observed in 100% (12/12), 41.7% (5/12), and 30% (3/10) in above three groups, respectively (Fig.). Size and number of lung metastatic tumor were significantly different between control and treatment groups (control vs single treatment group: p=0.0014; control vs triple treatment group: p=0.0007). In immunohistochemistry, phosphorylated Rb was decreased in lung tumor of treatment group as compared with that in control group. In both low and high dose groups, no remarkable change was found in body weight and blood analyses at early and late phase after m-p16 administration. No remarkable change was also observed histologically in bone marrow of treatment groups. CONCLUSIONS Systemic p16 delivery could prevent lung tumor development on mouse BT metastatic model without severe adverse events assessed by blood analyses and histological evaluation. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e608 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Toru Shimazui More articles by this author Kazuhiro Yoshikawa More articles by this author Jun Miyazaki More articles by this author Kazuhiko Uchida More articles by this author Atsushi Yamauchi More articles by this author Mikinobu Ohtani More articles by this author Hiroyuki Nishiyama More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...