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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.

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Effect of letrozole (0.7 μM) or/and radiotherapy (RT) on MCF-7CA cell-cycle progression. (a) Control cells were compared with (b) MCF-7CA cells harvested after exposure to letrozole. In the case of RT treatment, cells were harvested after RT (c) without or (d) with letrozole. Cells were fixed and stained with propidium iodide for flow cytometry analysis as described in Materials and methods. Percentages of the G0/G1 phase, the S phase, and the G2/M phase were determined by CellQUEST analysis software on the basis of DNA content of the histogram. Data represent mean values of duplicate samples. Similar results were obtained in replicate experiments.
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Figure 6: Effect of letrozole (0.7 μM) or/and radiotherapy (RT) on MCF-7CA cell-cycle progression. (a) Control cells were compared with (b) MCF-7CA cells harvested after exposure to letrozole. In the case of RT treatment, cells were harvested after RT (c) without or (d) with letrozole. Cells were fixed and stained with propidium iodide for flow cytometry analysis as described in Materials and methods. Percentages of the G0/G1 phase, the S phase, and the G2/M phase were determined by CellQUEST analysis software on the basis of DNA content of the histogram. Data represent mean values of duplicate samples. Similar results were obtained in replicate experiments.

Mentions: The effect of letrozole treatment on cell-cycle phase distribution in the MCF-7CA cell line was evaluated using flow cytometry (Fig. 6). Treatment with 0.7 μM letrozole for 6 days induced accumulation of cells in the G1 phase (77.5 ± 1.5%), with a significant decrease in the percentage of cells in the S phase (9.0 ± 1%) relative to controls (20.4 ± 0.7%). No cells with subdiploid DNA content were observed, demonstrating that letrozole does not induce apoptosis in these cell lines.


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)

Effect of letrozole (0.7 μM) or/and radiotherapy (RT) on MCF-7CA cell-cycle progression. (a) Control cells were compared with (b) MCF-7CA cells harvested after exposure to letrozole. In the case of RT treatment, cells were harvested after RT (c) without or (d) with letrozole. Cells were fixed and stained with propidium iodide for flow cytometry analysis as described in Materials and methods. Percentages of the G0/G1 phase, the S phase, and the G2/M phase were determined by CellQUEST analysis software on the basis of DNA content of the histogram. Data represent mean values of duplicate samples. Similar results were obtained in replicate experiments.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 6: Effect of letrozole (0.7 μM) or/and radiotherapy (RT) on MCF-7CA cell-cycle progression. (a) Control cells were compared with (b) MCF-7CA cells harvested after exposure to letrozole. In the case of RT treatment, cells were harvested after RT (c) without or (d) with letrozole. Cells were fixed and stained with propidium iodide for flow cytometry analysis as described in Materials and methods. Percentages of the G0/G1 phase, the S phase, and the G2/M phase were determined by CellQUEST analysis software on the basis of DNA content of the histogram. Data represent mean values of duplicate samples. Similar results were obtained in replicate experiments.
Mentions: The effect of letrozole treatment on cell-cycle phase distribution in the MCF-7CA cell line was evaluated using flow cytometry (Fig. 6). Treatment with 0.7 μM letrozole for 6 days induced accumulation of cells in the G1 phase (77.5 ± 1.5%), with a significant decrease in the percentage of cells in the S phase (9.0 ± 1%) relative to controls (20.4 ± 0.7%). No cells with subdiploid DNA content were observed, demonstrating that letrozole does not induce apoptosis in these cell lines.

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