Premium
Bikunin plus paclitaxel markedly reduces tumor burden and ascites in mouse model of ovarian cancer
Author(s) -
Kobayashi Hiroshi,
Yagyu Tatsuo,
Inagaki Kiyokazu,
Kondo Toshiharu,
Suzuki Mika,
Kanayama Naohiro,
Terao Toshihiko
Publication year - 2004
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.20082
Subject(s) - paclitaxel , ascites , ovarian cancer , medicine , oncology , chemotherapy , cancer
Our previous studies of intraperitoneal ovarian carcinoma in a mouse model demonstrated that bikunin gene transfection could prevent ascites formation and intraperitoneal disseminated metastasis. Although ascites was almost completely inhibited, tumor burden was variably reduced. Several reports have indicated that bikunin may be involved in tumor survival. In the present study, the effectiveness of exogenous bikunin and the biodistribution characteristics of 125 I‐bikunin were initially examined in a mouse model of human ovarian cancer HRA cells. The once‐daily i.p . administration of bikunin significantly decreased progressive growth of HRA tumors and ascites formation in a dose‐dependent manner. Maximal radioisotope tumor uptake peaked at 7.4% injected dose/g at 3 hr. Bikunin binding specificity was demonstrated by reduced tumor uptake after coinjection of excess nonradioactive bikunin. Bikunin was rapidly excreted renally. The bikunin therapy produced the significant inhibition in expression of the proteolysis (uPA and uPAR) and angiogenesis‐related molecules (VEGF and bFGF). The second purpose of our study was to optimize the antimetastatic activity of bikunin in combination with paclitaxel against HRA cells growing orthotopically in mice. The once‐daily i.p . administration of bikunin (25 μg/g body weight/day) in combination with paclitaxel ( i.p ., 100 μg/20 g at days 2 and 5) significantly decreased progressive growth of HRA cells in a synergistic fashion. In conclusion, combination therapy with bikunin plus paclitaxel may be an effective way to markedly reduce i.p . tumor growth and ascites in ovarian carcinoma possibly through suppression of uPA, uPAR, VEGF and bFGF expression. © 2004 Wiley‐Liss, Inc.