We evaluated the mechanism of antitumor effects of buserelin, which is one of LH-RH agonists, on a hormone dependent breast cancer model, using 7,12-dimethylbenz(a)anthracene (DMBA)-induced rat mammary cancer. Rats developing solid mammary tumors within 5-7 weeks following the DMBA administration were divided into groups weekly, and treated without delay. The tumor bearing rats were randomized into five groups with regard to tumor size or average weight (15 rats per group). Each group received one of the following treatments during 4 weeks: a) no treatment (NT); b) ovariectomy (Ovx); c) buserelin; d) Ovx and 17beta-estradiol (E2) (Ovx+E2); e) Ovx+E2+buserelin. Tumor regression immediately began at one week after both buserelin treatment and ovariectomy. A significant reduction of tumor size was observed in both buserelin-treated rats and Ovx rats compared with NT rats (p<0.01). No significant difference of tumor size was observed between buserelin-treated rats and ovariectomized rats. No reduction of tumor size was observed in Ovx+E2 rats and Ovx+E2+buserelin rats. Although the mean uterine wet weight of the buserelin group was significantly higher than that of the Ovx group, it was significantly lower than that of the NT group. The mean uterine wet weight of the NT group, the Ovx+E2 group and the Ovx+E2+buserelin group was similar and was significantly higher than that of the Ovx group. Buserelin did not inhibit exogenous estrogen-dependent tumor growth in DMBA-induced rat mammary cancers. These results suggest that buserelin has no direct effects on DMBA-induced rat mammary cancers, and the main mechanism of action of buserelin for tumor-reduction is due to ovarian estrogen deficiency.

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