COMPARATIVE STUDY OF HUMAN BREAST CARCINOMA MCF-7 CELLS DIFFERING IN THEIR RESISTANCE TO DOXORUBICIN: EFFECT OF IONIZING RADIATION ON APOPTOSIS AND TGF-b PRODUCTION

Chorna Inna, Bilyy Rostyslav, Datsyuk Leonid, Stoika Rostyslav

Aim: The aim of the study was to investigate the survival and growth of human breast carcinoma MCF-7 cells with different sensitivity to doxorubicin and production of transforming growth factor b-(TGF-b) in dependence on the dose- and duration of X-ray in order to check if the cross-resistance to doxorubicin and radiation effects exists. Methods: Determination of cell number and valiability using trypan blue (0.1% (w/v)) exclusion method, Western blot analysis of p53 protein expression, biological testing of TGF-b activity, lectinocytochemical analysis for apoptosis quantitative estimation in unirradiated and irradiated cells of both sublines of MCF-7 cells — sensitive (MCF-7(wt)) and resistant (MCF-7(DOX/R)) to doxorubicin. Results: It was found that doxorubicin-resistant breast cancer cells were also more refractory to X-radiation-dependent growth inhibition. There were revealed different effects of distinct doses of X-ray on p53 protein expression by cells of both sublines. The level of production of TGF-b was compared in non-irradiated MCF-7 cells and in these cells exposed to X-radiation. It was shown that X-radiation increased TGF-b activity in the conditioned medium of the irradiated cells of both doxorubicin-sensitive and -resistant lines. Conclusions: The results of our study suggest that the biological effects of X-radiation on human breast cancer MCF-7 cells can be at least partly mediated by TGF-b. Taking into account that TGF-b is a potent natural immunosupressor, one may consider that an increased activity of this cytokine can intensify negative effects of X-radiation.

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