Koo K L, Tejwani G A, Abou-Issa H
Department of Pharmacology, College of Medicine, Ohio State University, Columbus 43210, USA.
Anticancer Res. 1996 Jul-Aug;16(4A):1893-8.
We have shown earlier that naltrexone, a long acting opioid antagonist, inhibits the development and growth of 7,12-dimethylbenz(a)anthracene (DMBA)-induced rat mammary tumors. We extended these studies to determine the independent effects of naltrexone when fed at 75 mg/kg diet during the initiation (I), promotion (P), or initiation plus promotion (I+P) phases of DMBA-induced rat mammary carcinogenesis. The percentage of rats with palpable tumors as well as the number of tumors per rat were determined during the 130 day experiment. When fed during the 1, P, or I+P phases, mammary tumor incidence was significantly inhibited by 27%, 60% and 45% respectively, as compared to the control group. Similarly, tumor multiplicity was significantly reduced by naltrexone treatment. Tumor multiplicity was reduced by 40%, 73%, and 70% when fed naltrexone during I, P, and I+P respectively, as compared to the controls. These results indicate that naltrexone acts on the I and P phases, with the effects being maximal when fed during the P and I+P phases.
我们先前已表明，长效阿片类拮抗剂纳曲酮可抑制7,12-二甲基苯并(a)蒽（DMBA）诱导的大鼠乳腺肿瘤的发生和生长。我们扩展了这些研究，以确定在DMBA诱导的大鼠乳腺癌发生的起始（I）、促癌（P）或起始加促癌（I+P）阶段，以75 mg/kg饮食给予纳曲酮时的独立作用。在为期130天的实验中，测定了可触及肿瘤的大鼠百分比以及每只大鼠的肿瘤数量。与对照组相比，在I、P或I+P阶段给予纳曲酮时，乳腺肿瘤发生率分别显著降低了27%、60%和45%。同样，纳曲酮治疗显著降低了肿瘤多发性。与对照组相比，在I、P和I+P阶段给予纳曲酮时，肿瘤多发性分别降低了40%、73%和70%。这些结果表明，纳曲酮作用于起始和促癌阶段，在P和I+P阶段给予时效果最佳。
