Inhibition of fibroblast growth factor 2-induced apoptosis involves survivin expression, protein kinase Cα activation and subcellular translocation of Smac in human small cell lung cancer cells
Desheng Xiao
Department of Pathology, Xiangya School of Medicine, Central South University, Changsha 410013, China
These authors contributed equally to this work
Search for more papers by this authorKuansong Wang
Department of Pathology, Xiangya School of Medicine, Central South University, Changsha 410013, China
These authors contributed equally to this work
Search for more papers by this authorCorresponding Author
Jianhua Zhou
Department of Pathology, Xiangya School of Medicine, Central South University, Changsha 410013, China
*Corresponding author: Tel, 86-731-2650406; Fax, 86-731-2650406; E-mail, [email protected]Search for more papers by this authorHuiqiu Cao
Department of Pathology, Xiangya School of Medicine, Central South University, Changsha 410013, China
Search for more papers by this authorZhenghao Deng
Department of Pathology, Xiangya School of Medicine, Central South University, Changsha 410013, China
Search for more papers by this authorYongbin Hu
Department of Pathology, Xiangya School of Medicine, Central South University, Changsha 410013, China
Search for more papers by this authorXiahui Qu
Department of Pathology, Xiangya School of Medicine, Central South University, Changsha 410013, China
Search for more papers by this authorJifang Wen
Department of Pathology, Xiangya School of Medicine, Central South University, Changsha 410013, China
Search for more papers by this authorDesheng Xiao
Department of Pathology, Xiangya School of Medicine, Central South University, Changsha 410013, China
These authors contributed equally to this work
Search for more papers by this authorKuansong Wang
Department of Pathology, Xiangya School of Medicine, Central South University, Changsha 410013, China
These authors contributed equally to this work
Search for more papers by this authorCorresponding Author
Jianhua Zhou
Department of Pathology, Xiangya School of Medicine, Central South University, Changsha 410013, China
*Corresponding author: Tel, 86-731-2650406; Fax, 86-731-2650406; E-mail, [email protected]Search for more papers by this authorHuiqiu Cao
Department of Pathology, Xiangya School of Medicine, Central South University, Changsha 410013, China
Search for more papers by this authorZhenghao Deng
Department of Pathology, Xiangya School of Medicine, Central South University, Changsha 410013, China
Search for more papers by this authorYongbin Hu
Department of Pathology, Xiangya School of Medicine, Central South University, Changsha 410013, China
Search for more papers by this authorXiahui Qu
Department of Pathology, Xiangya School of Medicine, Central South University, Changsha 410013, China
Search for more papers by this authorJifang Wen
Department of Pathology, Xiangya School of Medicine, Central South University, Changsha 410013, China
Search for more papers by this authorThis work was supported by the Natural Science Foundation of Hunan Province (No. 06JJ2098)
Abstract
To investigate the mechanism by which fibroblast growth factor 2 (FGF-2) inhibits apoptosis in the human small cell lung cancer cell line H446 subjected to serum starvation, apoptosis was evaluated by flow cytometry, Hoechst 33258 staining, caspase-3 activity, and DNA fragmentation. Survivin expression induced by FGF-2 and protein kinase Cα (PKCα) translocation was detected by subcellular frac-tionation and Western blot analysis. In addition, FGF-2-in-duced release of Smac from mitochondria to the cytoplasm was analyzed by Western blotting and immunofluorescence. FGF-2 reduced apoptosis induced by serum starvation and up-regulated survivin expression in H446 cells in a dose-dependent andtime-dependentmanner, andinhibitedcaspase-3 activity. FGF-2 also inhibited the release of Smac from mitochondria to the cytoplasm induced by serum starvation and increased PKCα translocation from the cytoplasm to the cell membrane. In addition, PKC inhibitor inhibited the expression of survivin. FGF-2 up-regulates the expression of survivin protein in H446 cells and blocks the release of Smac from mitochondria to the cytoplasm. PKCα regulated FGF-2-induced survivin expression. Thus, survivin, Smac, and PKCα might play important roles in the inhibition of apoptosis by FGF-2 in human small cell lung cancer cells.
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