Abstract
Aim:
The aim was to study the anti-tumor activities and mechanisms of two synthetic peptide fragments of tumstatin (alpha3 (IV) NC1 domain) in human gastric carcinoma cells in vitro and in vivo.
Methods:
MTT assay and cell cycle assay were used to study the anti-tumor and anti-angiogenic activities of two peptide fragments in vitro. Apoptosis induced by the two peptide fragments was demonstrated by TUNEL assay and morphological observation. The orthotopic tumor model was established to investigate the activities of two peptide fragments in vivo. Intratumor vascularization and the expressions of VEGF, bFGF, Fas, FasL, Bax, Bcl-2, and caspase 3 were determined using immunohistochemistry and Western blot analysis.
Results:
Peptide 19 inhibited SGC-7901 proliferation and induced apoptosis both in vitro and in vivo. Notably, peptide 21 suppressed the proliferation of HUVEC-12 cells in vitro. Each peptide arrested both cell lines at the G0/G1 phase of the cell cycle, and they also synergistically suppressed in vitro and in vivo tumor growth. Immunohistochemistry and Western blot analysis revealed the strong expression of Fas, FasL and caspase 3 in orthotopic tumor tissues treated with peptide 19 alone or in combination with peptide 21. Decreased expressions of VEGF and bFGF and decreased microvessel density (MVD) in orthotopic tumor tissues were seen in mice treated with peptide 21 alone or in combination with peptide 19.
Conclusion:
Two tumstatin peptide fragments facilitate two unique antitumor activities. Thus, they are drug candidates in the treatment of gastric carcinoma.
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Acknowledgements
This work was supported by a grant from the National Natural Science Foundation of China (No 30472035), the Key Program of Heilongjiang Science and Technology Foundation (ZJY04-0102), Heilongjiang Innovation Program in Graduate Education (YJSCX2007-0201HLJ), a grant from the Department of Education of Heilongjiang Province (11531089), and the Youth Program of Heilongjiang Science and Technology Foundation (QC08C07).
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Li, Yj., Sun, Lc., He, Y. et al. The anti-tumor properties of two tumstatin peptide fragments in human gastric carcinoma. Acta Pharmacol Sin 30, 1307–1315 (2009). https://doi.org/10.1038/aps.2009.111
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DOI: https://doi.org/10.1038/aps.2009.111
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