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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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Aromatase activity in MCF-7 wild-type (wt) and MCF-7CA transfected cell lines. Aromatase activity was measured by the tritiated water assay. Treatment with letrozole inhibited the 40 nM 1β-3H-androstenedione substrate conversion. Open bars, filled bars, and grey bars represent background radioactivity, aromatase activity without treatment, and aromatase activity after treatment with letrozole (100 nM), respectively.
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Figure 1: Aromatase activity in MCF-7 wild-type (wt) and MCF-7CA transfected cell lines. Aromatase activity was measured by the tritiated water assay. Treatment with letrozole inhibited the 40 nM 1β-3H-androstenedione substrate conversion. Open bars, filled bars, and grey bars represent background radioactivity, aromatase activity without treatment, and aromatase activity after treatment with letrozole (100 nM), respectively.

Mentions: The aromatase activity was induced by the androgenic substrate Δ4 androstenedione at a 40 nM concentration. The effects of letrozole on aromatase activity in cultured breast cancer cells are shown in Fig. 1. In the MCF-7CA transfected cell line, letrozole (100 nM) markedly inhibited aromatase activity.


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)

Aromatase activity in MCF-7 wild-type (wt) and MCF-7CA transfected cell lines. Aromatase activity was measured by the tritiated water assay. Treatment with letrozole inhibited the 40 nM 1β-3H-androstenedione substrate conversion. Open bars, filled bars, and grey bars represent background radioactivity, aromatase activity without treatment, and aromatase activity after treatment with letrozole (100 nM), respectively.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 1: Aromatase activity in MCF-7 wild-type (wt) and MCF-7CA transfected cell lines. Aromatase activity was measured by the tritiated water assay. Treatment with letrozole inhibited the 40 nM 1β-3H-androstenedione substrate conversion. Open bars, filled bars, and grey bars represent background radioactivity, aromatase activity without treatment, and aromatase activity after treatment with letrozole (100 nM), respectively.
Mentions: The aromatase activity was induced by the androgenic substrate Δ4 androstenedione at a 40 nM concentration. The effects of letrozole on aromatase activity in cultured breast cancer cells are shown in Fig. 1. In the MCF-7CA transfected cell line, letrozole (100 nM) markedly inhibited aromatase activity.

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