Blockage of angiotensin II type I receptor decreases the synthesis of growth factors and induces apoptosis in C6 cultured cells and C6 rat glioma

Abstract

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 AT 1 receptor of angiotensin inhibites tumour growth, cell proliferation and angiogenesis of C6 rat glioma. The aim of this study was to study the effects of the blockage of AT 1 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 À1 to rats with C6 glioma significantly decreased tumoral volume and production of plateletderived growth factor, vascular endothelial growth factor and basic fibroblast growth factor. It also induced apoptosis in a dosedependent 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 AT 1 diminishes tumoral growth through inhibition of growth factors and promotion of apoptosis.

GPCRs and cancer

“…In this respect, ACE inhibitors and angiotensin II receptor blockers (ARBs) have recently acquired an increasing interest as chemopreventive agents [110,117,118] . Of note, ARBs have been associated with reduced cancer occurrence in patients with essential hypertension and a longer exposure to ARBs has been related with major benefits in cancer patients [119] .…”

Decreased Expression of Angiotensin-Converting Enzyme 2 in Pancreatic Ductal Adenocarcinoma Is Associated with Tumor Progression

“…ACE is preferentially expressed in PDAC (Arafat et al 2007), and ACE exerts an important role in the occurrence of PDAC through the formation of ANG II. Evidence for the involvement of the ACE-ANG II-AT1R pathway in the pathogenesis of PDAC, such as growth, metastasis, and angiogenesis, has accumulated in recent reports (Egami et al 2003;Arrieta et al 2005).…”

Expression of AT1 and AT2 angiotensin receptors in astrocytomas is associated with poor prognosis

“…Likewise, the presence of AT1 and AT2 in C6 glioma cells has been described, showing that their blockage can inhibit tumoral growth and angiogenesis (Rivera et al, 2001;Fogarty et al, 2002;Arrieta et al, 2005). Recent reports describe the local expression of many components of RAAS in several human neoplasms, among these human GM (Deshayes and Nahmias, 2005).…”

“…In previous reports, the presence of AT1 was documented in rat astrocytoma cells (Fogarty et al, 2002). Our group has also shown that selective blockage of AT1 inhibits tumour growth, cell proliferation, and angiogenesis by inducing apoptosis in C6 rat malignant glioma (Arrieta et al, 2005), suggesting that AT1 plays a significant role in tumour angiogenesis and growth. In this study, we show the expression of ANGII receptors and their participation in the prognosis of patients with astrocytomas.…”