Effects of steroid hormones and opioid peptides on the growth of androgen-responsive Shionogi carcinoma (SC115) cells in primary culture.

Abstract

We investigated the effects of dihydrotestosterone (DHT), hydrocortisone (HC), basic fibroblast growth factor (bFGF), and opioid peptides on the growth of cells from the androgen-responsive Shionogi mouse mammary carcinoma (SC115) in primary culture. Androgen-responsive SC115 tumor 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- and bFGF-induced growth. Three opioid agonists, beta-endorphin (beta-EP), cyclazocine, and morphine sulfate, markedly inhibited SC115 tumor cell growth at concentrations ranging from 10(-11) to 10(-7) M in serum-containing medium with or without DHT, HC, or bFGF, with the greatest inhibition occurring in medium with DHT. In serum-free medium, beta-EP had no inhibitory effects on cell growth. However, beta-EP at concentrations of 10(-9) M or greater significantly inhibited cell growth in serum-free medium containing DHT, HC, or bFGF, with the greatest inhibition 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 manner by DHT, HC, or bFGF in both serum-containing and serum-free media. It appears that bFGF may mediate, at least partially, DHT-stimulated cell growth. In addition, the opioid peptide system may be involved in regulating endocrine control of growth of the androgen-responsive SC115 carcinoma. The dose-responsive inhibitory effects of opioids and their reversal by naloxone suggest that these effects may be mediated by opioid receptors.