Abstract
The effect of captopril on tumour growth was examined in a xenograft model of human renal cell carcinoma (RCC). Inoculation of the human RCC cell line SN12K-1 (10(6) cells) under the left kidney capsule of severe combined immunodeficient (SCID) mice resulted in the growth of large tumours, with an increase in weight of the inoculated kidney of 3.69+/-1.63-fold (mean+/-s.d.) when compared with the contralateral normal kidney. In mice treated with captopril (19 mg kg(-1) day(-1) or 94 mg kg(-1) day(-1) administered in the drinking water), there was a significant dose-related reduction in tumour development; the tumour bearing kidneys weighed 1.9+/-0.42 and 1.55+/-0.42 times the normal kidneys, respectively (P< 0.05 compared with untreated animals). In vitro, captopril at clinically achievable doses (0.1-10 microM) had no significant effect on the incorporation of [3H]thymidine into SN12K-1 cells. Thus, this highly significant attenuation by captopril of in vivo tumour growth does not appear to be due to a direct effect on the proliferation of the tumour cells. Further studies are required to determine the mechanism of inhibition of tumour growth by captopril, in particular to evaluate the role of angiotensin II in this process.
Full text
PDF



Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Antonaccio M. J., Rubin B., Horovitz Z. P., Laffan R. J., Goldberg M. E., High J. P., Harris D. N., Zaidi I. Effects of chronic treatment with captopril (SQ 14,225), an orally active inhibitor of angiotensin I-converting enzyme, in spontaneously hypertensive rats. Jpn J Pharmacol. 1979 Apr;29(2):285–294. doi: 10.1254/jjp.29.285. [DOI] [PubMed] [Google Scholar]
- Burris J. F. The expanding role of angiotensin converting enzyme inhibitors in the management of hypertension. J Clin Pharmacol. 1995 Apr;35(4):337–342. doi: 10.1002/j.1552-4604.1995.tb04070.x. [DOI] [PubMed] [Google Scholar]
- Chobanian M. C., Julin C. M. Angiotensin II stimulates ammoniagenesis in canine renal proximal tubule segments. Am J Physiol. 1991 Jan;260(1 Pt 2):F19–F26. doi: 10.1152/ajprenal.1991.260.1.F19. [DOI] [PubMed] [Google Scholar]
- Cogan M. G. Angiotensin II: a powerful controller of sodium transport in the early proximal tubule. Hypertension. 1990 May;15(5):451–458. doi: 10.1161/01.hyp.15.5.451. [DOI] [PubMed] [Google Scholar]
- Douglas J. G. Angiotensin receptor subtypes of the kidney cortex. Am J Physiol. 1987 Jul;253(1 Pt 2):F1–F7. doi: 10.1152/ajprenal.1987.253.1.F1. [DOI] [PubMed] [Google Scholar]
- Fernandez L. A., Twickler J., Mead A. Neovascularization produced by angiotensin II. J Lab Clin Med. 1985 Feb;105(2):141–145. [PubMed] [Google Scholar]
- Folkman J., Klagsbrun M. Angiogenic factors. Science. 1987 Jan 23;235(4787):442–447. doi: 10.1126/science.2432664. [DOI] [PubMed] [Google Scholar]
- Giudicelli J. F., Richer C., Freslon J. L., Glasson S., Decourt S. Effets comparés des betabloquants et du captopril sur le développement de l'hypertension génétique chez le rat. Arch Mal Coeur Vaiss. 1981 Jun;74(Spec No):51–59. [PubMed] [Google Scholar]
- Goldfarb D. A., Diz D. I., Tubbs R. R., Ferrario C. M., Novick A. C. Angiotensin II receptor subtypes in the human renal cortex and renal cell carcinoma. J Urol. 1994 Jan;151(1):208–213. doi: 10.1016/s0022-5347(17)34918-2. [DOI] [PubMed] [Google Scholar]
- Goligorsky M. S., Osborne D., Howard T., Hruska K. A., Karl I. E. Hormonal regulation of gluconeogenesis in cultured proximal tubular cells: role of cytosolic calcium. Am J Physiol. 1987 Nov;253(5 Pt 2):F802–F809. doi: 10.1152/ajprenal.1987.253.5.F802. [DOI] [PubMed] [Google Scholar]
- Harris P. J. Regulation of proximal tubule function by angiotensin. Clin Exp Pharmacol Physiol. 1992 Apr;19(4):213–222. doi: 10.1111/j.1440-1681.1992.tb00441.x. [DOI] [PubMed] [Google Scholar]
- Johnston C. I., Fabris B., Jandeleit K. Intrarenal renin-angiotensin system in renal physiology and pathophysiology. Kidney Int Suppl. 1993 Jul;42:S59–S63. [PubMed] [Google Scholar]
- Jonsson J. R., Head R. J., Frewin D. B. Effect of alpha 1-adrenoceptor blockade on the development of hypertension in the spontaneously hypertensive rat. Eur J Pharmacol. 1992 Feb 11;211(2):263–268. doi: 10.1016/0014-2999(92)90538-f. [DOI] [PubMed] [Google Scholar]
- Le Noble F. A., Hekking J. W., Van Straaten H. W., Slaaf D. W., Struyker Boudier H. A. Angiotensin II stimulates angiogenesis in the chorio-allantoic membrane of the chick embryo. Eur J Pharmacol. 1991 Mar 26;195(2):305–306. doi: 10.1016/0014-2999(91)90552-2. [DOI] [PubMed] [Google Scholar]
- Le Noble F. A., Schreurs N. H., van Straaten H. W., Slaaf D. W., Smits J. F., Rogg H., Struijker-Boudier H. A. Evidence for a novel angiotensin II receptor involved in angiogenesis in chick embryo chorioallantoic membrane. Am J Physiol. 1993 Feb;264(2 Pt 2):R460–R465. doi: 10.1152/ajpregu.1993.264.2.R460. [DOI] [PubMed] [Google Scholar]
- Mancilla-Jimenez R., Stanley R. J., Blath R. A. Papillary renal cell carcinoma: a clinical, radiologic, and pathologic study of 34 cases. Cancer. 1976 Dec;38(6):2469–2480. doi: 10.1002/1097-0142(197612)38:6<2469::aid-cncr2820380636>3.0.co;2-r. [DOI] [PubMed] [Google Scholar]
- Norman J., Badie-Dezfooly B., Nord E. P., Kurtz I., Schlosser J., Chaudhari A., Fine L. G. EGF-induced mitogenesis in proximal tubular cells: potentiation by angiotensin II. Am J Physiol. 1987 Aug;253(2 Pt 2):F299–F309. doi: 10.1152/ajprenal.1987.253.2.F299. [DOI] [PubMed] [Google Scholar]
- Pfeffer M. A., Braunwald E., Moyé L. A., Basta L., Brown E. J., Jr, Cuddy T. E., Davis B. R., Geltman E. M., Goldman S., Flaker G. C. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. Results of the survival and ventricular enlargement trial. The SAVE Investigators. N Engl J Med. 1992 Sep 3;327(10):669–677. doi: 10.1056/NEJM199209033271001. [DOI] [PubMed] [Google Scholar]
- Reddy M. K., Baskaran K., Molteni A. Inhibitors of angiotensin-converting enzyme modulate mitosis and gene expression in pancreatic cancer cells. Proc Soc Exp Biol Med. 1995 Dec;210(3):221–226. doi: 10.3181/00379727-210-43942. [DOI] [PubMed] [Google Scholar]
- Volpert O. V., Ward W. F., Lingen M. W., Chesler L., Solt D. B., Johnson M. D., Molteni A., Polverini P. J., Bouck N. P. Captopril inhibits angiogenesis and slows the growth of experimental tumors in rats. J Clin Invest. 1996 Aug 1;98(3):671–679. doi: 10.1172/JCI118838. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wolf G., Neilson E. G. Angiotensin II induces cellular hypertrophy in cultured murine proximal tubular cells. Am J Physiol. 1990 Nov;259(5 Pt 2):F768–F777. doi: 10.1152/ajprenal.1990.259.5.F768. [DOI] [PubMed] [Google Scholar]
- Wolf G. Regulating factors of renal tubular hypertrophy. Clin Investig. 1993 Oct;71(10):867–870. doi: 10.1007/BF00190340. [DOI] [PubMed] [Google Scholar]
- Wolf G., Zahner G., Mondorf U., Schoeppe W., Stahl R. A. Angiotensin II stimulates cellular hypertrophy of LLC-PK1 cells through the AT1 receptor. Nephrol Dial Transplant. 1993;8(2):128–133. [PubMed] [Google Scholar]
- Wolf G., Ziyadeh F. N., Zahner G., Stahl R. A. Angiotensin II-stimulated expression of transforming growth factor beta in renal proximal tubular cells: attenuation after stable transfection with the c-mas oncogene. Kidney Int. 1995 Dec;48(6):1818–1827. doi: 10.1038/ki.1995.480. [DOI] [PubMed] [Google Scholar]

