Letrozole sensitizes breast cancer cells to ionizing radiation.
Details
State: Public
Version: Final published version
License: Not specified
Serval ID
serval:BIB_A4CAE8B80263
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Letrozole sensitizes breast cancer cells to ionizing radiation.
Journal
Breast cancer research
ISSN
1465-542X (Electronic)
ISSN-L
1465-5411
Publication state
Published
Issued date
2005
Peer-reviewed
Oui
Volume
7
Number
1
Pages
R156-63
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Publication Status: ppublish
Abstract
Radiotherapy (RT) is considered a standard treatment option after surgery for breast cancer. Letrozole, an aromatase inhibitor, is being evaluated in the adjuvant setting. We determined the effects of the combination of RT and letrozole in the aromatase-expressing breast tumour cell line MCF-7CA, stably transfected with the CYP19 gene.
Irradiations were performed using a cobalt-60 source with doses ranging from 0 to 4 Gy. Cells were incubated with androstenedione in the presence or absence of letrozole. Effects of treatment were evaluated using clonogenic assays, tetrazolium salt colorimetric (MTT) assays, and cell number determinations. Cell-cycle analyses were conducted using flow cytometry.
The survival fraction at 2 Gy was 0.66 for RT alone and was 0.44 for RT plus letrozole (P = 0.02). Growth of MCF-7CA cells as measured by the cell number 6 days after radiotherapy (2 and 4 Gy) was decreased by 76% in those cells treated additionally with letrozole (0.7 microM) compared with those receiving radiotherapy alone (P = 0.009). Growth inhibition, assessed either by cell number (P = 0.009) or by the MTT assay (P = 0.02), was increased after 12 days of the combination treatment. Compared with radiation alone, the combination of radiation and letrozole produced a significant decrease in radiation-induced G2 phase arrest and a decrease of cells in the S phase, with cell redistribution in the G1 phase.
These radiobiological results may form the basis for concurrent use of letrozole and radiation as postsurgical adjuvant therapy for breast cancer.
Irradiations were performed using a cobalt-60 source with doses ranging from 0 to 4 Gy. Cells were incubated with androstenedione in the presence or absence of letrozole. Effects of treatment were evaluated using clonogenic assays, tetrazolium salt colorimetric (MTT) assays, and cell number determinations. Cell-cycle analyses were conducted using flow cytometry.
The survival fraction at 2 Gy was 0.66 for RT alone and was 0.44 for RT plus letrozole (P = 0.02). Growth of MCF-7CA cells as measured by the cell number 6 days after radiotherapy (2 and 4 Gy) was decreased by 76% in those cells treated additionally with letrozole (0.7 microM) compared with those receiving radiotherapy alone (P = 0.009). Growth inhibition, assessed either by cell number (P = 0.009) or by the MTT assay (P = 0.02), was increased after 12 days of the combination treatment. Compared with radiation alone, the combination of radiation and letrozole produced a significant decrease in radiation-induced G2 phase arrest and a decrease of cells in the S phase, with cell redistribution in the G1 phase.
These radiobiological results may form the basis for concurrent use of letrozole and radiation as postsurgical adjuvant therapy for breast cancer.
Keywords
Antineoplastic Agents/pharmacology, Aromatase/biosynthesis, Aromatase/genetics, Breast Neoplasms/pathology, Cell Cycle/drug effects, Cell Cycle/radiation effects, Cell Survival, Female, Flow Cytometry, Humans, Letrozole, Nitriles/pharmacology, Radiation-Sensitizing Agents/pharmacology, Radiotherapy, Adjuvant, Transfection, Triazoles/pharmacology
Pubmed
Web of science
Open Access
Yes
Create date
24/01/2008 18:16
Last modification date
09/08/2024 16:04