EFFECTS OF STEROID-HORMONES AND OPIOID-PEPTIDES ON THE GROWTH OF ANDROGEN-RESPONSIVE SHIONOGI CARCINOMA (SC115) CELLS IN PRIMARY CULTURE

We investigated the effects of dihydrotestosterone (DHT), hydrocortiso ne (HC), basic fibroblast growth factor (bFGF), and opioid peptides on the growth of cells from the androgen-responsive Shionogi mouse mamma ry carcinoma (SC115) in primary culture. Androgen-responsive SC115 tum or cells were stimulated to grow in response to DHT, HC, and bFGF in a dose-responsive manner in both serum-containing and serum-free media. Moreover, anti-bFGF antibody had a marked inhibitory effect on DHT- a nd bFGF-induced growth. Three opioid agonists, beta-endorphin (beta-EP ), cyclazocine, and morphine sulfate, markedly inhibited SC115 tumor c ell growth at concentrations ranging from 10(-11) to 10(-7) M in serum . containing medium with or without DHT, HC, or bFGF, with the greates t inhibition occurring in medium with DHT. In serum-free medium, beta- EP had no inhibitory effects on cell growth. However, beta-EP at conce ntrations of 10(-9) M or greater significantly inhibited cell growth i n serum-free medium containing DHT, HC, or bFGF, with the greatest inh ibition again occurring in medium with DHT. Naloxone (10(-8) and 10(-6 ) M), an opioid receptor antagonist, blocked the inhibitory effects of beta-EP and morphine sulfate. These results suggest that SC115 tumor cells in primary culture are stimulated to grow in a dose-responsive m anner by DHT, HC, or bFGF in both serum-containing and serum-free medi a. It appears that bFGF may mediate, at least partially, DHT-stimulate d cell growth. In addition, the opioid peptide system may be involved in regulating endocrine control of growth of the androgen-responsive S C115 carcinoma. The dose-responsive inhibitory effects of opioids and their reversal by naloxone suggest that these effects may be mediated by opioid receptors.