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Cancer radiotherapie : journal de la Societe francaise de radiotherapie oncologique

Optimal combination of radiotherapy and endocrine drugs in breast cancer treatment.


PMID 23664221

Abstract

Breast cancer is the most common cancer in women. Radiotherapy is considered a standard treatment option after surgery and adjuvant endocrine therapy is also universally used. Tamoxifen and letrozole are the current first-line endocrine therapy drugs. However, information has been scarce about how best to sequence these therapies to maximize their effectiveness and keep toxic effects to a minimum. In this study, we observed the effect of different sequence combination of radiotherapy and endocrine drugs, tamoxifen or letrozole, to get the best treatment sequence. The combination effect of radiotherapy and tamoxifen was observed on breast tumour cell line MCF-7, radiotherapy and letrozole on aromatase-expressing breast tumour cell line MCF-7CA. Irradiation was performed with 6Gy, except for doses ranging from 0 to 8Gy for clone formation assay. Tamoxifen or letrozole was added before or after irradiation, respectively. Radiosensitivity was evaluated by clonogenic assay, cell viability by 3-(4,-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay. To explore the potential mechanism, cell apoptosis was determined by DNA-binding dye 4',6-diamidino-2-phenylindole dihydrochloride (DAPI) assay, the change of Bcl-2 and Bax expression was by western blot. Although no significant statistical difference was observed between different sequence, tamoxifen and letrozole both increased radiosensitivity. Furthermore, the above inhibitory effect was related with apoptosis signaling pathway, especially Bcl-2 and Bax. Taken together, these results suggested that endocrine drugs, such as tamoxifen and letrozole, have potential application with radiotherapy.