Captopril inhibits tumour growth in a xenograft model of human renal cell carcinoma.
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.
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Department of Surgery, University of Queensland, Princess Alexandra Hospital, Woolloongabba, Australia.
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Gotley
D C
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Thompson
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Green
M K
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Jonsson
J R
JR
D000704:Analysis of Variance; D000818:Animals; D000970:Antineoplastic Agents; D002216:Captopril / Q000494:pharmacology* / Q000627:therapeutic use; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000473:pathology*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D002216:Captopril