Open AccessAnti‐tumor effect of lentivirus‐mediated gene transfer of alphastatin on human glioma
Author(s) -
Guo ShiWen,
Che HongMin,
Li WenZhi
Publication year - 2011
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2011.01879.x
Subject(s) - angiogenesis , basic fibroblast growth factor , cancer research , vascular endothelial growth factor , glioma , mapk/erk pathway , secretion , fibroblast growth factor , biology , growth factor , vascular endothelial growth factor a , in vivo , kinase , chemistry , microbiology and biotechnology , endocrinology , receptor , vegf receptors , biochemistry
Alphastatin, an endogenous angiogenesis inhibitor, has recently been used as an anticancer agent in several tumor models. This study was to investigate whether local sustained long‐term expression of alphastatin could serve to diminish tumor growth of a human xenograft glioma model. We found that the recombinant alphastatin lentiviruses were able to stably infect HUVECs, and infected HUVECs could sustainably secrete alphastatin, which exhibited potent inhibitory effects on HUVECs migration, differentiation but not proliferation induced by vascular endothelial growth factor (VEGF) or basic fibroblast growth factor(bFGF). And the expression of secreted protein alphastatin markedly decreased tumor vascularization and inhibited tumor growth. Additionally, alphastatin inhibited VEGF‐ or bFGF‐induced initial stage of angiogenesis by reducing JNk and ERK phosphorylation in vitro . Taken together, these data demonstrate that secreted protein alphastatin inhibits VEGF‐ or bFGF‐induced angiogenesis by suppressing JNK and ERK kinases activation pathways in HUVECs, and markedly inhibits tumor angiogenesis in vivo . Consequently lentivirus‐mediated gene transfer might represent an effective strategy for expression of alphastatin to achieve inhibition of human malignant glioma proliferation and tumor progression. ( Cancer Sci 2011; 102: 1038–1044)