The present study was undertaken to evaluate the efficacy of using
steroid hormone antagonists tamoxifen and
Ru486 for
chemotherapy or
chemoprevention of
choriocarcinoma or other less malignant
gestational trophoblastic diseases (GTDs) such as
invasive mole. Using 4 trophoblast cell lines, we have shown that
tamoxifen (>/= 2 microM) has anti-growth activity on the
choriocarcinoma cell line BeWo but not on the other cell lines in a time and dose dependent manner while
Ru486 invariably had no detectable effect. Based on a radioimmunoassay, we have been able to detect low levels of
estrogen receptors on BeWo (6 +/- 0.4 fm/mg; Kd=438+/- 73 pM) and JEG-3 (6.55 +/- 1.2 fm/mg; Kd=710 +/- 42 pM) cells and
progesterone receptors on HT (48.62 fm/mg; Kd=1,690 +/- 182 pM) and TL (8.46 fm/mg; Kd=1,540 +/- 115 pM) cells. However, there is no definite correlation between
steroid responsiveness and the presence of the receptors. The mechanism of our observed
tamoxifen-mediated anti-cellular effect is uncertain and characteristics commonly associated with apoptotic cell death were not observed. The level of neither wild-type nor mutant forms of the p53
protein correlated with sensitivity to
tamoxifen. Our results suggest that
estrogen may be a
growth hormone for some trophoblasts and
tamoxifen may be potentially useful for the treatment of selected cases of
choriocarcinoma or other trophoblastic diseases.