Limits...
Letrozole sensitizes breast cancer cells to ionizing radiation.

Azria D, Larbouret C, Cunat S, Ozsahin M, Gourgou S, Martineau P, Evans DB, Romieu G, Pujol P, Pèlegrin A - Breast Cancer Res. (2004)

Bottom Line: 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.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).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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Radiation Oncology, CRLC Val d'Aurelle, Montpellier, France. azria@valdorel.fnclcc.fr

ABSTRACT

Introduction: 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.

Methods: 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.

Results: 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.

Conclusions: These radiobiological results may form the basis for concurrent use of letrozole and radiation as postsurgical adjuvant therapy for breast cancer.

Show MeSH

Related in: MedlinePlus

Growth inhibition with letrozole alone. (a) Seven nanomolar letrozole did not inhibit the growth of MCF-7CA cells during 18 days of incubation, whereas (b) 0.7 μM letrozole resulted in about 50% inhibition after 6, 12, and 18 days of incubation. Results are from cell-count assays.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC1064115&req=5

Figure 2: Growth inhibition with letrozole alone. (a) Seven nanomolar letrozole did not inhibit the growth of MCF-7CA cells during 18 days of incubation, whereas (b) 0.7 μM letrozole resulted in about 50% inhibition after 6, 12, and 18 days of incubation. Results are from cell-count assays.

Mentions: The cytotoxic effects of several concentrations of letrozole (7 nM–0.7 μM) on asynchronous, exponentially growing MCF-7CA cells were determined by cell-count assay. Letrozole at a concentration of 7 nM did not inhibit the growth of MCF-7CA cells during 18 days of incubation, whereas 0.7 μM resulted in about 50 ± 10% inhibition after 6, 12, and 18 days of incubation (Fig. 2). No effect of letrozole was seen on MCF-7 wild-type cells.


Letrozole sensitizes breast cancer cells to ionizing radiation.

Azria D, Larbouret C, Cunat S, Ozsahin M, Gourgou S, Martineau P, Evans DB, Romieu G, Pujol P, Pèlegrin A - Breast Cancer Res. (2004)

Growth inhibition with letrozole alone. (a) Seven nanomolar letrozole did not inhibit the growth of MCF-7CA cells during 18 days of incubation, whereas (b) 0.7 μM letrozole resulted in about 50% inhibition after 6, 12, and 18 days of incubation. Results are from cell-count assays.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1064115&req=5

Figure 2: Growth inhibition with letrozole alone. (a) Seven nanomolar letrozole did not inhibit the growth of MCF-7CA cells during 18 days of incubation, whereas (b) 0.7 μM letrozole resulted in about 50% inhibition after 6, 12, and 18 days of incubation. Results are from cell-count assays.
Mentions: The cytotoxic effects of several concentrations of letrozole (7 nM–0.7 μM) on asynchronous, exponentially growing MCF-7CA cells were determined by cell-count assay. Letrozole at a concentration of 7 nM did not inhibit the growth of MCF-7CA cells during 18 days of incubation, whereas 0.7 μM resulted in about 50 ± 10% inhibition after 6, 12, and 18 days of incubation (Fig. 2). No effect of letrozole was seen on MCF-7 wild-type cells.

Bottom Line: 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.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).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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Radiation Oncology, CRLC Val d'Aurelle, Montpellier, France. azria@valdorel.fnclcc.fr

ABSTRACT

Introduction: 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.

Methods: 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.

Results: 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.

Conclusions: These radiobiological results may form the basis for concurrent use of letrozole and radiation as postsurgical adjuvant therapy for breast cancer.

Show MeSH
Related in: MedlinePlus