Impact of DHT, IL-6 and IL-8 on proliferation of epithelial ovarian carcinoma cells in vitro
Objective To investigate the reciprocal regulation of androgen and cytokines in the growth of epithelial ovarian carcinoma. Methods The expression of androgen receptor (AR), interleukin 6 receptor (IL-6R) and interleukin 8 receptor (IL-8R) in five epithelial ovarian carcinoma cell lines was detected by Western blot and reverse transcription polymerase chain reaction (RT-PCR). Ovarian carcinoma cells expressing AR and IL-6R and IL-8R were selected for research. MTT assay was performed to investigate the effect of 5α-dihydrotestosterone (DHT), IL-6 and IL-8 on the proliferation of the above cells. Results (1) The expression of AR, IL-6Rα, gp130, IL-8RA and IL-8RB in five epithelial ovarian carcinoma cell lines was different. (2) In SKOV-3 cells, a low dose of DHT (0.1-1 nmol/L) inhibited cell proliferation, whereas a moderate- and high- dose of that (1-100 nmol/L) obviously promoted at 72, 96 and 120 h. For OVCAR-3 cells, DHT had no effect on cell proliferation at 48 h, while DHT markedly enhanced cell proliferation at 96 h and 144 h. The effect of DHT on two cells was in a time- and dose-dependent manner. (3) Flutamide (Flu), an AR inhibitor completely blocked DHT-enhanced cell proliferation, but IL-6-neutralizing antibody and IL-8-neutralizing antibody partially blocked DHT-stimulated cell proliferation. (4) IL-6 and IL-8 significantly promoted SKOV-3 and OVCAR-3 cell proliferation in a time- and dose-dependent manner, and both have a synergistic effect in SKOV-3 cells but not in OVCAR-3 cells. IL-6- and IL-8-promoted cell proliferation was completely blocked by specific neutralizing antibodies but not by isotype goat IgG. Conclusion The mechnism of androgen-induced ovarian carcinoma cell proliferation appears to be resulted from the direct action of androgen and the indirect regulation of cytokines (such as IL-6 and IL-8) and /or their receptors.