Blockage of angiotensin II type I receptor decreases the synthesis of growth factors and induces apoptosis in C6 cultured cells and C6 rat glioma.
Angiotensin II (Ang II) is a main effector peptide in the renin-angiotensin system and participates in the regulation of vascular tone. It also has a role in the expression of growth factors that induce neovascularisation which is closely associated to the growth of malignant gliomas. We have shown that the selective blockage of the AT1 receptor of angiotensin inhibits tumour growth, cell proliferation and angiogenesis of C6 rat glioma. The aim of this study was to study the effects of the blockage of AT1 receptor on the synthesis of growth factors, and in the genesis of apoptosis in cultured C6 glioma cells and in rats with C6 glioma. Administration of losartan at doses of 40 or 80 mg kg(-1) to rats with C6 glioma significantly decreased tumoral volume and production of platelet-derived growth factor, vascular endothelial growth factor and basic fibroblast growth factor. It also induced apoptosis in a dose-dependent manner. Administration of Ang II increased cell proliferation of cultured C6 cells which decreased by the administration of losartan. Our results suggest that the selective blockage of AT1 diminishes tumoral growth through inhibition of growth factors and promotion of apoptosis.
Arrieta
O
O
Neuroimmunology Unit of the National Institute of Neurology and Neurosurgery of Mexico, Insurgentes Sur 3877, 14269 Mexico City, Mexico. ogar@servidor.unam.mx
Guevara
P
P
Escobar
E
E
García-Navarrete
R
R
Pineda
B
B
Sotelo
J
J
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis; D001932:Brain Neoplasms / Q000473:pathology*; D005910:Glioma / Q000473:pathology*; D006133:Growth Substances / Q000096:biosynthesis*; D051381:Rats; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects* / Q000502:physiology*; D014407:Tumor Cells, Cultured
D047228:Angiotensin II Type 1 Receptor Blockers; D006133:Growth Substances; D044140:Receptor, Angiotensin, Type 1