Tamoxifen inhibits GH3 cell growth in culture via enhancement of apoptosis.
OBJECTIVE
To investigate the antitumor effects of tamoxifen on pituitary tumor GH3 cells, which lack receptors for dopamine.


METHODS
GH3 cells were treated with tamoxifen (10(-7) mol/L), bromocriptine (10(-8) mol/L), or a combination of tamoxifen and bromocriptine in serum-free media. The cell number, bromodeoxyuridine (BrdU) labeling ratio, and apoptotic ratio were assessed. Prolactin (PRL) expression was examined using immunocytochemistry and Western blot analysis.


RESULTS
After tamoxifen treatment for 4 days, the cell number decreased to 53.0% of that of untreated control cells. The percentage of PRL-immunoreactive GH3 cells decreased to 2.9%, versus 8.6% of untreated control cells, which was compatible with the results of Western blot analysis for PRL. Apoptosis increased to approximately three times that of untreated control cells at Day 2 of treatment, whereas no significant change was shown in BrdU incorporation. These effects by tamoxifen were not observed in the simultaneous treatment with 17beta-estradiol. Bromocriptine did not change the cell number, BrdU incorporation, the apoptotic ratio, or the percentage of PRL-positive cells, and it was also shown that tamoxifen did not change the sensitivity of GH3 cells to bromocriptine treatment.


CONCLUSIONS
Tamoxifen, an antiestrogen, exerts its antitumor effect on GH3 cells in two ways: by suppression of cell growth and by causing a decrease in PRL. Apoptosis seems to contribute to the inhibition of GH3 cell growth.
Lee
S Y
SY
Department of Anatomy, Seoul National University College of Medicine, Korea.
Ahn
B T
BT
Baik
S H
SH
Lee
B L
BL
D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001971:Bromocriptine / Q000494:pharmacology; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects*; D018491:Dopamine Agonists / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D006801:Humans; D008854:Microscopy, Electron; D009381:Neoplasms, Radiation-Induced; D010911:Pituitary Neoplasms; D011388:Prolactin / Q000378:metabolism; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects; D013629:Tamoxifen / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D018931:Antineoplastic Agents, Hormonal; D018491:Dopamine Agonists; D011954:Receptors, Dopamine; D013629:Tamoxifen; D001971:Bromocriptine; D004958:Estradiol; D011388:Prolactin