INHIBITORY EFFECT OF DEXAMETHASONE AND PROGESTERONE IN-VITRO ON PROLIFERATION OF HUMAN RENAL-CELL CARCINOMAS AND EFFECTS ON EXPRESSION OF INTERLEUKIN-6 OR INTERLEUKIN-6 RECEPTOR
J. Takenawa et al., INHIBITORY EFFECT OF DEXAMETHASONE AND PROGESTERONE IN-VITRO ON PROLIFERATION OF HUMAN RENAL-CELL CARCINOMAS AND EFFECTS ON EXPRESSION OF INTERLEUKIN-6 OR INTERLEUKIN-6 RECEPTOR, The Journal of urology, 153(3), 1995, pp. 858-862
Interleukin-6 (IL-6) has been suggested as an autocrine growth factor
of human renal cell carcinomas. Since steroids are known to inhibit IL
-6 gene expression, we investigated their effects on the growth of ren
al cell carcinoma. Dexamethasone inhibited proliferation of 2 of 4 ren
al cell carcinoma cell lines in a dose-dependent manner. In one of the
se 2 cell lines, IL-6 gene expression was also inhibited, but not in t
he other. The inhibitory effect of dexamethasone on cell proliferation
was not reversed by the exogenous IL-6. In 1 of the 2 remaining cell
lines, the inhibition of IL-6 gene expression was observed, although t
here was no inhibition of cell proliferation. Thus, inhibition of grow
th by dexamethasone did not correlate with an inhibitory action of dex
amethasone on IL-6 mRNA expression. Progesterone inhibited the growth
of 1 cell line without concomitant inhibition of IL-6 gene expression.
Expression of IL-6 receptor mRNA was not altered. A dose-dependent in
crease in mRNA expression of gp130, the transducer of IL-6 signal, was
induced by dexamethasone and progesterone in 2 and 1 of the 4 cell li
nes, respectively. These data suggest that, in some renal cell carcino
mas, steroids may inhibit cell proliferation by a mechanism independen
t of their effects on mRNA expression of IL-6 and IL-6 receptors. Dexa
methasone may be useful, not only for palliation of paraneoplastic syn
drome caused by overproduction of IL-6, but also for inhibition of gro
wth of renal cell carcinomas.