[Effects of a novel antiprogestin derivative ZXH951 on proliferation and telomerase activity of human breast carcinoma cell lines].
OBJECTIVE
To investigate the antiproliferative activity of a new synthetic steroid ZXH951 structurally related to mifepristone (RU486) and its effects on cell cycle traverse and telomerase activity in human breast carcinoma cell lines.


METHODS
Antiproliferative activity was determined by cell growth curve, MTT reduction and colony formation. Receptor binding affinities were measured by competitive binding assay using radiolabelled ligands. Cell cycle distribution was analyzed by flow cytometry. Telomerase activity was investigated by TRAP-PCR.


RESULTS
ZXH951 exhibited potent antiproliferative activity in estrogen receptor and progesterone receptor positive human breast carcinoma cell lines in vitro, high affinity with human progesterone receptor-A, little affinity with estrogen receptor and blockade the cells in G1 phase. Moreover, when T47D cells were exposed to 0.4, 1.0 and 10 mumol.L-1 of ZXH951 for 72 h, the telomerase activity was significantly decreased.


CONCLUSIONS
ZXH951 is a promising progesterone receptor antagonist. It significantly inhibits the growth of estrogen receptor and progesterone receptor positive human breast carcinoma cells. Its mechanism of action may be related to its antiproliferation mediated by progesterone receptor and inhibition of telomerase activity.
Zhou
L E
LE
Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Han
R
R
D001943:Breast Neoplasms / Q000201:enzymology*; D005260:Female; D006727:Hormone Antagonists / Q000494:pharmacology*; D006801:Humans; D011980:Receptors, Progesterone / Q000037:antagonists & inhibitors*; D013256:Steroids / Q000494:pharmacology*; D019098:Telomerase / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D006727:Hormone Antagonists; D011980:Receptors, Progesterone; D013256:Steroids; C466503:ZXH951; D019098:Telomerase