title: bFGF rescues imatinib/STI571-induced apoptosis of sis-NIH3T3 fibroblasts.
abstract: PDGF-B-transfected, sis-NIH3T3 fibroblasts serve as a model system for examining the role of PDGF signaling in tumors. We have found that imatinib/STI571, a tyrosine kinase inhibitor targeting PDGF receptors, induces apoptosis of sis-NIH3T3 fibroblasts cultured under serum free conditions, which was rescued by the addition of 10% newborn calf serum (NCS). Therefore, growth factors included in serum were tested with regard to their ability to rescue imatinib-induced apoptosis. While PDGF-AB, EGF, and IGF-I failed to protect imatinib-induced sis-NIH3T3 cell apoptosis, bFGF rescued it. The effects of bFGF were confirmed by both cell viability assays and Bax/Bcl-2 gene expression ratio. An FGF receptor inhibitor, PD166866, invalidated the protective effect of bFGF. However, combination of imatinib and PD166866 failed to induce cell death of sis-NIH3T3 cells when cultured in 10% NCS. These results indicate that synergistic administration of some types of tyrosine kinase inhibitors need to be tested under in vivo-like conditions to establish novel strategies in anti-cancer therapy.
authors.affiliation: Department of Biochemistry, Nihon University School of Dentistry, 1-8-13 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-8310, Japan. oshima-m@dent.nihon-u.ac.jp
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Ohshima
authors.forename: Yoko
authors.initials: Y
authors.lastname: Yamaguchi
authors.forename: Kai
authors.initials: K
authors.lastname: Kappert
authors.forename: Patrick
authors.initials: P
authors.lastname: Micke
authors.forename: Kichibee
authors.initials: K
authors.lastname: Otsuka