Combined effects of lutenizing hormone-releasing hormone analogue with antiestrogen on rat mammary tumors.

The efficacy of luteining hormone-releasing hormone (LH-RH) analogue, buserelin, combind with tamoxifen (TAM) on 7,12-dimethylbenz(a)anthracene (DMBA)-induced rat mammary tumors was investigated. Low-dose of TAM (L-TAM), 1 mg/kg daily, significantly suppressed the growth of tumors compared with no treatment group. High-dose of TAM (H-TAM), 10 mg/kg daily, suppressed growth considerably, and there was a significant difference in the antitumor effect between the L-TAM group and the H-TAM group. The combined treatment using buserelin and L-TAM significantly suppressed the tumor growth compared with the treatment using each single agent. LH-RH analogue actually reduced serum estradiol (E2) levels and enhanced the antitumor effect brought by a therapeutical dose of TAM. The reduction of serum cholesterol levels as a beneficial effect of TAM was reserved when combined with buserelin. Insulin-like growth factor 1 (IGF-1) expressions in tumors were significantly decreased in the buserelin and L-TAM group. These results support the usefulness of this combination in clinical use.