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Fusion protein containing SH3 domain of c‐Abl induces hepatocarcinoma cells to apoptosis
Author(s) -
Yin Ji Kai,
Liang Ying Min,
He Xian Li,
Lu Jian Guo,
Zhang Li,
Bao Guo Qiang,
Ma Qing Jiu
Publication year - 2007
Publication title -
hepatology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.123
H-Index - 75
eISSN - 1872-034X
pISSN - 1386-6346
DOI - 10.1111/j.1872-034x.2007.00068.x
Subject(s) - fusion protein , apoptosis , abl , in vivo , microbiology and biotechnology , in vitro , breakpoint cluster region , sh3 domain , tunel assay , immunocytochemistry , biology , cell growth , chemistry , cancer research , proto oncogene tyrosine protein kinase src , signal transduction , biochemistry , endocrinology , receptor , tyrosine kinase , gene , recombinant dna
Aim: Through a preliminary test on a novel protein containing an HIV1‐TAT domain and a SH3 domain of oncoprotein P210 BCR‐ABL (we named it after PTD‐BCR/ABL SH3), we found that this protein shows inhibition activity of hepatocarcinoma cell HepG‐2. The purpose of the present study is to explore the biological behavior of PTD‐BCR/ABL SH3 fusion protein in hepatocarcinoma cells in vitro and in vivo . Methods: HepG‐2 cells were cocultured with the fusion protein for the indicated time and studied in vitro by immunocytochemistry staining to demonstrate the localization of the protein, light and electron microscope observation in morphology research, MTT assay to draw a growth curve and to analyze inhibition ratio, DNA ladder and TUNEL staining to study apoptosis. Nude mice bearing HepG‐2 tumors were used to test the antitumor activity of the fusion protein. Results: PTD‐BCR/ABL SH3 fusion protein successfully entered into HepG‐2 cells and localized in the nucleus. The protein had shown high cytotoxity through inducing HepG‐2 cells to apoptosis, and in vivo. The growth speed of tumors in the treatment group was distinctly slower than those in the control group, and the survival time of mice in the treatment group was longer than those in the control group. The growth of the tumors had been inhibited in the treatment group, while other tissues, such as heart, liver, lung and kidney displayed normal morphology. Conclusion: PTD‐BCR/ABL SH3 fusion protein displays significant inhibitory activity of inducing hepatocarcinoma HepG‐2 cells to apoptosis in vitro . It also showed therapeutic effects in vivo .