Hii S I, Nicol D L, Gotley D C, Thompson L C, Green M K, Jonsson J R
Department of Surgery, University of Queensland, Princess Alexandra Hospital, Woolloongabba, Australia.
Br J Cancer. 1998 Mar;77(6):880-3. doi: 10.1038/bjc.1998.145.
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.
在人肾细胞癌(RCC)异种移植模型中研究了卡托普利对肿瘤生长的影响。将人RCC细胞系SN12K - 1(10⁶个细胞)接种到严重联合免疫缺陷(SCID)小鼠的左肾包膜下,导致大肿瘤生长,与对侧正常肾脏相比,接种肾脏的重量增加了3.69±1.63倍(平均值±标准差)。在用卡托普利治疗的小鼠(通过饮用水给予19 mg kg⁻¹天⁻¹或94 mg kg⁻¹天⁻¹)中,肿瘤发展出现了显著的剂量相关减少;荷瘤肾脏的重量分别为正常肾脏的1.9±0.42倍和1.55±0.42倍(与未治疗动物相比,P<0.05)。在体外,临床可达到剂量(0.1 - 10 μM)的卡托普利对[³H]胸腺嘧啶掺入SN12K - 1细胞没有显著影响。因此,卡托普利对体内肿瘤生长的这种高度显著的抑制作用似乎不是由于对肿瘤细胞增殖的直接影响。需要进一步研究以确定卡托普利抑制肿瘤生长的机制,特别是评估血管紧张素II在此过程中的作用。