EXPRESSION OF BAX, BAD and BCL-2 PROTEINS UNDER X-RADIATION EFFECT TOWARDS HUMAN BREAST CARCINOMA MCF-7 CELLS AND THEIR DOXORUBICIN-RESISTANT DERIVATIVES

Chorna I.V., Datsyuk L.O., Stoika R.S.

Aim: 1) To investigate the effect of X-rays on expression of Bax, Bad, and Bcl-2 proteins in human breast carcinoma MCF-7 cells, sensitive (MCF-7(wt)) and resistant (MCF-7(DOX/R)) to doxorubicin; 2) to measure X-radiation-induced DNA damage in order to clarify if changes in the expression of those proteins and DNA repair capacity can be responsible for the development of drug-resistance and for altered radio-sensitivity of MCF-7(DOX/R) cells. Methods: Expression of Bax, Bad and Bcl-2 proteins was detected by Western-blot analysis. DNA damage induced by X-radiation and the kinetics of subsequent DNA repair were estimated by alkaline DNA comet assay. Results: We found an increase in the expression of pro-apoptotic Bax and Bad proteins and a decrease in the expression of Bcl-2 protein in MCF-7(wt) cells under the effect of X-radiation, whereas the expression of those proteins was not changed significantly in the irradiated MCF-7(DOX/R) cells. Different pattern of Bcl-2 expression was shown in MCF-7(DOX/R) cells compared with MCF-7(wt) cells. A decreased level of X-radiation-induced DNA damage and an increased DNA repair capacity were revealed in MCF-7(DOX/R) cells compared with MCF-7(wt) cells. Conclusions: The results of our study suggest that a reduced apoptotic response and an increased DNA repair capacity in MCF-7(DOX/R) cells might contribute to the resistance of these cells to X-radiation treatment.