Inhibition of fibroblast growth factor 2-induced apoptosis involves surviving expression, protein kinase Cα activation and subcellular translocation of Smac in human small cell lung cancer cells

Release time:2020-07-12

Affiliation of Author(s):中南大学

Teaching and Research Group:病理学系

Journal:Acta Biochim Biophy Sin

Key Words:FGF-2; survivin; Smac; PKC; apoptosis; lung cancer

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 fractionation and Western blot analysis. In addition, FGF-2-induced 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 and time-dependent manner, and inhibited caspase-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.

Co-author:Huiqiu Cao, Zhenghao Deng, Yongbin Hu, Xia-hui Qu, Jifang Wen

First Author:Desheng Xiao, Kuansong Wang

Indexed by:Journal paper

Correspondence Author:Jianhua Zhou

Issue:40

Page Number:297-303

Translation or Not:no

Date of Publication:2008-02-13