HIV protease inhibitors are potent anti-angiogenic molecules and promote regression of Kaposi sarcoma

被引:250
作者
Sgadari, C
Barillari, G
Toschi, E
Carlei, D
Bacigalupo, I
Baccarini, S
Palladino, C
Leone, P
Bugarini, R
Malavasi, L
Cafaro, A
Falchi, M
Valdembri, D
Rezza, G
Bussolino, F
Monini, P
Ensoli, B
机构
[1] Ist Super Sanita, Virol Lab, I-00161 Rome, Italy
[2] Ist Super Sanita, Epidemiol & Biostat Lab, I-00161 Rome, Italy
[3] Ist Super Sanita, Lab Ultrastruct, I-00161 Rome, Italy
[4] Univ Roma Tor Vergata, Dept Expt Med, Rome, Italy
[5] Univ Turin, Dept Oncol Sci, Inst Canc Res & Treatment, Turin, Italy
关键词
D O I
10.1038/nm0302-225
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Treatment with HIV-1 protease inhibitors (PI) is associated with a reduced incidence or regression of Kaposi sarcoma (KS). Here we show that systemic administration of the PIs indinavir or saquinavir to nude mice blocks the development and induces regression of angioproliferative KS-like lesions promoted by primary human KS cells, basic fibroblast growth factor (bFGF), or bFGF and vascular endothelial growth factor (VEGF) combined. These PIs also block bFGF or VEGF-induced angiogenesis in the chorioallantoic membrane assay with a potency similar to paclitaxel (Taxol). These effects are mediated by the inhibition of endothelial- and KS-cell invasion and of matrix metalloproteinase-2 proteolytic activation by PIs at concentrations present in plasma of treated individuals. As PIs also inhibit the in vivo growth and invasion of an angiogenic tumor-cell line, these data indicate that PIs are potent anti-angiogenic and anti-tumor molecules that might be used in treating non-HIV KS and in other HIV-associated tumors.
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页码:225 / 232
页数:8
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