bFGF rescues imatinib/STI571-induced apoptosis of sis-NIH3T3 fibroblasts

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• 作者：Mitsuhiro Ohshima ; Yoko Yamaguchi ; Kai Kappert ; Patrick Micke ; Kichibee Otsuka
• 关键词：sis ; Apoptosis ; Imatinib ; bFGF ; PDGF ; Escape-mechanism
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2009
• 出版时间：3 April 2009
• 年：2009
• 卷：381
• 期：2
• 页码：165-170
• 全文大小：583 K

文摘

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.