EFFECTS OF OK-432 (PICIBANIL) ON THE ESTROGEN-RECEPTORS OF MCF-7 CELLS AND POTENTIATION OF ANTIPROLIFERATIVE EFFECTS OF TAMOXIFEN IN COMBINATION WITH OK-432

OK-432 (picibanil), a streptococcal preparation, has a strong biologic al response modifier (BRM) function and is expected to produce clinica l improvement and prolongation of survival in treated cancer patients in Japan. We were interested in whether OK-432 augments estrogen recep tor (ER) levels in breast cancer. To investigate the effect of the BRM s on cellular growth and the characteristics of ER and progesterone re ceptors (PgR) in the human breast cancer cell line MCF-7, we used OK-4 32, Krestin (PSK), a protein-bound polysaccharide extracted from Corio lus versicolor, and lentinan, a fungal branched(1...3)-beta-D-glycan. OK432 and PSK dose dependently inhibited DNA synthesis of MCF-7 cells, and the 50% inhibitory concentrations of OK-432 and PSK were 1.2 KE ( Minische Einheit, clinical unit)/ml and 200 mu g/ml, respectively. Len tinan showed no direct anticancer effect in vitro. We found that OK-43 2 induced a 2-fold increase in ER levels in MCF-7 cells at 0.005 KE/ml , but not in PgR. Lentinan and low-dose PSK did not change ER or PgR l evels, but high-dose PSK decreased ER and PgR. We also studied the com bined effect of OK-432 and antiestrogens, tamoxifen (TAM) and DP-TAT-5 9. The combined treatment with OK-432 and TAM showed an additive inhib itory effect on MCF-7 cells. These results suggest that OK-432 may aug ment the therapeutic effect of TAM in breast cancer.