Differential effects of LHRH and somatostatin analogs on human breast cancer

We have been interested in the possible direct effects of luteinizing hormone releasing hormone (LHRH) and somatostatin (SS) analogs on the growth of human mammary tumor cells. Four recently synthesized peptide hormones including the LHRH agonists d-Trp6-LHRH and zoladex, LHRH antagonists SB30 and SB75, and the somatostatin analog RC 160 were analyzed for their effects on DNA synthesis of MCF-7 breast cancer cells in culture. At 48 hr, d-Trp6-LHRH and SB30 did not show significant effects (dose range, 10^-12-10^-6 m). However, the combination of these two peptides at 10^-10 m produced significant inhibition of ³[H]thymidine incorporation (50% control). At 72 hr in the absence of estradiol-stimulated growth, d-Trp6-LHRH showed inhibition at 10^-12 and 10^-10 m (P < 0.005 and 0.001). At higher concentrations, no significant inhibition was noted. In contrast to d-Trp6, SB30 (antagonist) showed no inhibition but significant stimulation of DNA synthesis at 10^-5 and 10^-4 m. In the presence of added estradiol (10^-9 m), complete reversal of d-Trp6-LHRH analog inhibition is noted. In contrast, there is persistent stimulation by SB30 (P < 0.001). At 96 hr, d-Trp6-LHRH continued to show maximal inhibition of 70% in the absence of estradiol. SB30 stimulated DNA synthesis 100% at 10^-6 m. At 72 hr, the SS analog RC 160 demonstrated significant inhibition (53%) that was similar to d-Trp6 and SB75 peptides. At 96 hr, RC 160 showed a biphasic response of stimulation at 10^-12-10^-10 m (P < 0.05) and inhibition at or above 10^-6 m. These results demonstrate direct effects of LHRH and somatostatin analogs on the in vitro growth of human breast cancer that are analog specific and concentration dependent.