Abstract
Malignancy of neoplasms is partly dependent on angiogenesis. Angiotensin II mediates angiogenesis and transcription of growth-related factors through stimulation of the AT1 receptor (AT1R). Losartan, a drug used mostly for treatment of hypertension, binds strongly to this receptor. We found the presence of AT1 receptor on C6 glioma cells and studied the effect of Losartan on the growth and angiogenesis of C6 rat glioma; Losartan in dose of 80 mg/kg induced 79% reduction of tumoural volume with a significant decrease of vascular density, mitotic index and cell proliferation. Our results demonstrate the conspicuous presence of AT1R in malignant glial cells and a favourable therapeutic response in experimental glioma by selective blockage of the AT1 receptor. © 2001 Cancer Research Campaign http://www.bjcancer.com
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References
Arrieta O, Guevara P, Reyes S, Ortiz A, Rembao D and Sotelo J (1998) Protamine inhibits angiogenesis and growth of C6 rat glioma; a synergistic effect when combined with carmustine. Eur J Cancer 34: 2101–2106
Burnier M (2001) Angiotensin II Type 1 Receptor Blockers. Circulation 103: 904–912
Chamczynski P and Sacchi N (1987) Single-step method of RNA isolation by acid guanidinium thyocianate–phenol chloroform extraction. Anal Biochem 162: 156–159
Chen L, Re RN, Prakash O and Mondal D (1991) Angiotensin-converting enzyme inhibition reduces neuroblastoma cell growth rate. Proc Soc Exp Biol Med 196: 280–283
Cheng SY, Huang HJ, Nagane M, Ji XD, Wang D, Shih CC, Arap W, Huang CM and Cavenee WK (1996) Suppression of glioblastoma angiogenicity and tumorigenicity by inhibition of endogenous expression of vascular endothelial growth factor. Proc Natl Acad Sci USA 93: 8502–8507
Chung O, Kuhl H, Stoll M and Unger T (1998) Physiological and pharmacological implications of AT1 versus AT2 receptors. Kidney Int Suppl 67: 595–599
DeAngelis LM (2001) Brain tumors. N Engl J Med 2: 114–123
Dzait VJ, Gibbons GH and Pratt RE (1991) Molecular mechanisms of vascular renin-angiotensin-system in myointimal hyperplasia. Hypertension 18, (Suppl II):100–105
Fernández LA, Twickler J and Mead A (1985) Neovascularization produced by angiotensin II. J Lab Clin Med 105: 141–145
Fournier A, Ghitu A, Darabont R, Mazouz H, Makadassi R, Canaple S, Rosa A and Fernandez LA (1999) Duality of angiotensin II receptors and risk for stroke and cancer: what is the connection?. Presse Med 28: 918–922
Fujimoto Y, Sasaki T, Tsuchida A and Chayama K (2001) Angiotensin II type 1 receptor expression in human pancreatic cancer and growth inhibition by angiotensin II type receptor antagonist. FEBS Lett 495: 197–200
González-Espinosa C and García-Sainz JA (1992) Angiotensin II and active phorbol esthers induce proto-oncogenes expression in isolated rat hepatocytes. Biochim Biophys Acta 1136: 309–314
Guevara P and Sotelo J (1999) C6 rat glioma grown into the peritoneal cavity, a large source of tumoral cells for subcutaneous transplant of glioma. J Neurooncol 44: 91–92
Hafizi S, Chester AH, Allen SP, Morgan K and Yacoub MH (1998) Growth response of human coronary smooth muscle cells to angiotensin II and influence of angiotensin AT1 receptor blockade. Coron Artery Dis 9: 167–175
Harris AL (1997) Antiangiogenesis for cancer therapy. Lancet 349, (Suppl 2):SII 13–15
Iwai N and Inagami T (1992) Identification of two subtypes in the rat type I angiotensin II receptor. FEBS Lett 298: 257–260
Jensen RL (1998) Growth factor-mediated angiogenesis in the malignant progression of glial tumors: a review. Surg Neurol 49: 189–195
Kawakara Y, Sunako M, Tsuda T, Fukuzaki H, Fukumoto Y and Takai Y (1988) Angiotensin II-induced espression of the c-fos gene through protein kinase C activation and calcium ion mobilization in cultured vascular smooth muscle cells. Biochem Biophys Res Commun 150: 52–59
Kim KJ, Li B, Winer J, Armanini M, Gillet N, Phillips HS and Ferrara N (1993) Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo. Nature 362: 841–844
Leung KH, Chang RS, Lotti VJ, Roscoe WA, Smith RD, Timmermans PB and Chiu AT (1992) AT1 receptor mediate the release of prostaglandins in porcine smooth muscle cells and rat astrocytes. Am J Hypertens 5: 648–656
Lever AF, Hole DJ, Gillis CR, McCallum IR, McInnes GT, McKinnon PL, Meredith PA, Murray LS, Reid JL and Robertson JW (1998) Do inhibitors of angiotensin-I-converting enzyme protect against risk of cancer?. Lancet 352: 179–184
Lund EL, Spang-Thomsen M, Skovgaard-Poulsen H and Kristjansen PE (1998) Tumor angiogenesis – a new therapeutic target in gliomas. Acta Neurol Scand 97: 52–62
Plate KH, Breier G and Risau W (1994a) Molecular mechanisms of developmental and tumor angiogenesis. Brain Pathol 4: 207–218
Plate KH, Breier G, Weich HA and Risau W (1994b) Vascular endothelial growth factor and glioma angiogenesis: coordinate induction of VEGF receptors, distribution of VEGF protein and possible in vivo regulatory mechanisms. Int J Cancer 59: 520–529
Roychowdhury DF, Tseng, Jr A, Fu KK, Weinberg V and Weidner N (1996) New Prognostic Factors in Nasopharyngeal Carcinoma. Cancer 77: 1419–1426
Schmidt NO, Westphal M, Hagel C, Ergun S, Stravrou D, Rosen EM and Lamszus K (1999) Levels of vascular endothelial growth factor, hepatocyte growth factor/scatter factor and basic fibroblast growth factor in human gliomas and their relation to angiogenesis. Int J Cancer 84: 10–18
Siragy H (1999) Angiotensin II receptor blockers: review of the binding characteristics. Am J Cardiol 84: 3S–8S
Stoll M, Meffert S, Stroth U and Unger T (1995a) Growth or antigrowth: angiotensin and the endothelium. J Hypertens 13: 1529–1534
Stoll M, Steckelings UM, Paul M, Bottari SP, Metzger R and Unger T (1995b) The Angiotensin AT2 receptor mediates inhibition of cell proliferation in coronary endothelial cells. J Clin Invest 95: 651–657
van der Valk P, Lindeman J and Kamphorst W (1997) Growth factor profiles of human gliomas. Do non-tumour cells contribute to tumour growth in glioma?. Ann Oncol 8: 1023–1029
Wang DH and Prewitt RL (1990) Captopril reduces aortic and microvascular growth in hypertensive and normotensive rats. Hypertension 15: 68–77
Wang D, Huang HJ, Kazlauskas A and Cavenee WK (1999) Induction of vascular endothelial growth factor expression in endothelial cells by platelet-derived growth factor through the activation of phosphatidylinositol 3-kinase. Cancer Res 59: 1464–1472
Weidner N, Semple JP, Welch WR and Folkman J (1991) Tumor Angiogenesis and Metastasis–Correlation in Invasive Breast Carcinoma. New Eng J Med 324: 1–8
Workman P, Twentyman P, Balkwill F, Balmain A, Chaplin D, Double J, Embleton J, Newell D, Raymond R, Stables J, Stephens T and Wallace J (1998) United Kingdom Co-ordinating Committee on Cancer Research (UKCCCR) Guidelines for the Welfare of Animals in Experimental Neoplasia (Second Edition). Br J Cancer 77: 1–10
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Rivera, E., Arrieta, O., Guevara, P. et al. AT1 receptor is present in glioma cells; its blockage reduces the growth of rat glioma. Br J Cancer 85, 1396–1399 (2001). https://doi.org/10.1054/bjoc.2001.2102
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DOI: https://doi.org/10.1054/bjoc.2001.2102
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