CAPTOPRIL INHIBITS TUMOR-GROWTH IN A XENOGRAFT MODEL OF HUMAN RENAL-CELL CARCINOMA

The effect of captopril on tumour growth was examined in a xenograft m odel of human renal cell carcinoma (RCC). Inoculation of the human RCC cell line SN12K-1 (10(6) cells) under the left kidney capsule of seve re combined immunodeficient (SCID) mice resulted in the growth of larg e tumours, with an increase in weight of the inoculated kidney of 3.69 +/- 1.63-fold (mean +/- s.d.) when compared with the contralateral no rmal kidney. In mice treated with captopril (19 mg kg(-1) day(-1) or 9 4 mg kg(-1) day(-1) administered in the drinking water), there was a s ignificant dose-related reduction in tumour development; the tumour be aring kidneys weighed 1.9 +/- 0.42 and 1.55 +/- 0.42 times the normal kidneys, respectively (P < 0.05 compared with untreated animals). In v itro, captopril at clinically achievable doses (0.1-10 mu M) had no si gnificant effect on the incorporation of [H-3]thymidine into SN12K-1 c ells. Thus, this highly significant attenuation by captopril of in viv o tumour growth does not appear to be due to a direct effect on the pr oliferation of the tumour cells. Further studies are required to deter mine the mechanism of inhibition of tumour growth by captopril, in par ticular to evaluate the role of angiotensin II in this process.