Tamoxifen induced apoptosis in ZR-75 breast cancer xenografts antedates tumour regression.
The ZR-75-1 ER positive breast cancer cell line, xenografted in female nude mice, has been used to determine the effect of tamoxifen on cell proliferation (as measured by mitosis) and cell death (as evidenced by apoptosis and necrosis). After 2 days treatment, there was a significant rise in apoptosis (p < 0.05), whereas a fall in mitosis was not apparent until 7 days (p < 0.05). Furthermore there was an increase in the apoptotic:mitotic ratio on day 7 (p < 0.05). These changes antedated tumour regression, which did not reach not significance until day 14. Tamoxifen did not increase necrosis (which significantly decreased in treated tumours once they had regressed (p < 0.01). In contrast tamoxifen treatment of xenografted MDA-MB-231 ER-negative breast cancer cells produced no significant effects on growth, apoptosis, or mitosis. This study presents clear evidence for tamoxifen inducing apoptosis in ZR-75-1 xenografts (but not MDA-MB-231 tumours). Since changes in apoptosis and mitosis antedate tumour regression, their assessment may provide the potential by which to predict tumour response to tamoxifen therapy.
Cameron
D A
DA
I.C.R.F. Medical Oncology Unit, Western General Hospital, Edinburgh, UK.
Ritchie
A A
AA
Langdon
S
S
Anderson
T J
TJ
Miller
W R
WR
D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D017209:Apoptosis; D001943:Breast Neoplasms / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D005260:Female; D051379:Mice; D008819:Mice, Nude; D008940:Mitotic Index / Q000187:drug effects; D009368:Neoplasm Transplantation; D013629:Tamoxifen / Q000494:pharmacology*; D013997:Time Factors; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D018931:Antineoplastic Agents, Hormonal; D013629:Tamoxifen