Expression of Bax, Bad and Bcl-2 proteins under x-radiation effect towards human breast carcinoma MCF-7 cells and their doxorubicin-resistant derivatives.
OBJECTIVE
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.
Chorna
I V
IV
Institute of Cell Biology, National Academy of Sciences of Ukraine, Lviv 79005, Ukraine.
Datsyuk
L O
LO
Stoika
R S
RS
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000473:pathology*; D002277:Carcinoma / Q000473:pathology*; D020552:Comet Assay; D004249:DNA Damage; D004260:DNA Repair; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D004591:Electrophoresis, Polyacrylamide Gel; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects*; D006801:Humans; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis; D051025:bcl-Associated Death Protein / Q000096:biosynthesis
D000903:Antibiotics, Antineoplastic; C494819:BAD protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein; D004317:Doxorubicin