Abstract | INTRODUCTION: METHOD: In vitro, the concentrations required to reduce cell numbers by 50% (50% inhibitory concentration) were established (MDA-MB231, MCF-7, MCF-7/HER2-18, BT-474, SK-BR3 and SKOV3). Human DCIS was implanted in nude mice or, in separate experiments, cultured cells were injected (MDA-MB231, MCF-7/HER2-18, SKOV3) and allowed to form tumours. Proliferation and apoptosis were determined by immunohistochemistry in xenografts and cell tumours. RESULTS: The 50% inhibitory concentrations varied a hundred-fold, from 39 nmol/l (+/- 26 nmol/l) for SKBR3 to 5.9 micromol/l(+/- 0.8 micromol/l) for MDA-MB231. In MCF-7/HER2-18 and SKOV3 cells the levels of tumour growth inhibition were approximately 85% and 40%, respectively. There was a significant decrease in the cell turnover index (CTI; proliferation/apoptosis). In MDA-MB 231 with activated k-ras no inhibition was observed. In treated DCIS xenografts proliferation decreased and apoptosis increased. The CTI ratio between the start and 1 and 2 weeks of treatment were 1.99 and 1.50, respectively, for controls and 0.85 (P = 0.005) and 0.75 (P = 0.08) for treated xenografts. CONCLUSION: Treatment with the farnesyl transferase inhibitor reduced cell growth in vitro and cell tumour growth in vivo. In DCIS treatment resulted in a reduced CTI. R115777 is a promising treatment for breast cancer but the relation between effect and growth factor receptor and ras status has to be established.
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Authors | Fredrik Wärnberg, Daniel White, Elizabeth Anderson, Fiona Knox, Robert B Clarke, Julie Morris, Nigel J Bundred |
Journal | Breast cancer research : BCR
(Breast Cancer Res)
Vol. 8
Issue 2
Pg. R21
( 2006)
ISSN: 1465-542X [Electronic] England |
PMID | 16611371
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Quinolones
- Farnesyltranstransferase
- tipifarnib
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Topics |
- Animals
- Breast Neoplasms
(drug therapy, pathology)
- Calcinosis
(pathology)
- Carcinoma, Intraductal, Noninfiltrating
(drug therapy, pathology)
- Cell Division
(drug effects)
- Cell Line, Tumor
- Farnesyltranstransferase
(antagonists & inhibitors)
- Female
- Humans
- Mammography
- Mice
- Mice, Inbred BALB C
- Mice, Nude
- Ovarian Neoplasms
(drug therapy, pathology)
- Quinolones
(therapeutic use)
- Transplantation, Heterologous
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