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. 2005 Apr 11;92(7):1247-52.
doi: 10.1038/sj.bjc.6602483.

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

O Arrieta  1 , P Guevara, E Escobar, R García-Navarrete, B Pineda, J Sotelo
Affiliations

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

O Arrieta et al. Br J Cancer. .

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 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.

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Figures

Figure 1
Figure 1
Effect of losartan administration at doses of 40 and 80 mg Kg−1 on the apoptotic rate in tissue sections of C6 glioma (TUNEL stain). A significant increase of the apoptosis was observed with losartan treatment at 80 mg Kg−1.
Figure 2
Figure 2
Effect of the blockage of AT1 receptor with losartan on the contents of PDGF, FGF, VEGF and HGF in C6 rat glioma. A significant reduction in the concentration of PDGF, FGF and VEGF was obtained with losartan treatment.
Figure 3
Figure 3
Effects of the administration of Ang II (10−7 M), losartan (10−5 M), or Ang II plus losartan on cultured C6 cells. During the initial 12 h of treatment, there was a significant reduction of viability in the cells treated with Ang II plus losartan; in contrast, after 48 h, a significant increase of viability was observed in the cells treated with Ang II alone.
Figure 4
Figure 4
Effects of Ang II (10−7 M), losartan (10−5 M) and Ang II plus losartan on apoptosis in cultured glioma C6 cells measured either by flow cytometry (A) or by ELISA (B). In both determinations the cells treated with losartan plus Ang II showed an increase of apoptosis during the initial hours after treatment.
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References

    1. Andrade SP, Cardoso CC, Machado RD, Beraldo WT (1996) Angiotensin-II induced angiogenesis in sponge implants in mice. Int J Microcirc Clin Exp 16: 302–307 - PubMed
    1. Ariza A, Fernandez LA, Inagami T, Kim JH, Manuelidis EE (1988) Renin in glioblastoma multiforme and its role in neovascularization. Am J Clin Pathol 90: 341–437 - PubMed
    1. Arrieta O, Garcia E, Guevara P, Garcia NR, Ondarza R, Rembao D, Sotelo J (2002) Hepatocyte growth factor is associated with poor prognosis of malignant gliomas and is a predictor for recurrence of meningioma. Cancer 94: 3210–3218 - PubMed
    1. Arrieta O, Guevara P, Reyes S, Ortiz A, Rembao D, Sotelo J (1998) Protamine inhibits angiogenesis and growth of C6 rat glioma; a synergistic effect when combined with carmustine. Eur J Cancer 34: 2102–2106 - PubMed
    1. Arrieta O, Guevara P, Reyes S, Palencia G, Rivera E, Sotelo J (2001) Paradoxical effect of aspirin on the growth of C6 rat glioma and on time of development of ENU-induced tumors of the nervous system. J Cancer Res Clin Oncol 127: 681–686 - PubMed

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