title: Connexin 43-dependent tumor-suppressing effect of the Bowman-Birk protease inhibitor on M5076 ovarian sarcoma-bearing mice.
abstract: The present study was designed to confirm whether the Bowman-Birk inhibitor (BBI) induces an increase in p27 accumulation without S phase kinase-associated protein 2 (skp2) degradation by means of the expression of connexin (Cx) 43 as a gap junctional intercellular communication (GJIC)-dependent pathway in mice with M5076 ovarian sarcoma. M5076 ovarian sarcomas (1x105 cells/animal) were subcutaneously transplanted onto the backs of BDF1 mice receiving 10, 20 or 40 mg/kg of purified BBI intraperitoneally. Relative tumor weight (p<0.01, r=0.503) was negatively correlated with the dose of BBI. In contrast, the relative density of Cx43 mRNA (p<0.01, r=0.570) and Cx43 (p<0.01, r=0.718) was positively correlated with the dose of BBI, as were p21 (p<0.01, r=0.633), p27 (p<0.01, r=0.561) and skp2 (p<0.01, r=0.733). We therefore suggest that the anti-carcinogenic effects of BBI induce negative growth control by means of an increase in p27 accumulation caused by the expression of Cx43 as a GJIC pathway.
authors.affiliation: Department of Veterinary Medicine, College of Bioresource Sciences, Nihon University, 1866 Kameino, Japan.
authors.forename: Noritaka
authors.initials: N
authors.lastname: Sakurai
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Suzuki
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Nagaoka
authors.forename: Teruyoshi
authors.initials: T
authors.lastname: Saito
authors.forename: Hisashi
authors.initials: H
authors.lastname: Yoshimura
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Yano
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Sadzuka
authors.forename: Ryuji
authors.initials: R
authors.lastname: Asano