Tamoxifen-mediated anti-cellular effect against a choriocarcinoma cell line.
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.
Ho
C K
CK
Department of Medical Research, Veterans General Hopsital-Taipei, Shih-Pai, Taipei, 11217, Taiwan, R.O.C.
Chi
C W
CW
Yu
K J
KJ
Wang
S Y
SY
D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D002822:Choriocarcinoma; D004965:Estrogen Antagonists / Q000633:toxicity; D005260:Female; D006727:Hormone Antagonists / Q000633:toxicity; D006801:Humans; D007700:Kinetics; D015735:Mifepristone / Q000633:toxicity; D011247:Pregnancy; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D013629:Tamoxifen / Q000633:toxicity*; D014327:Trophoblasts / Q000166:cytology / Q000187:drug effects; D014594:Uterine Neoplasms
D004965:Estrogen Antagonists; D006727:Hormone Antagonists; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013629:Tamoxifen; D015735:Mifepristone