Epirubicin up-regulates PARP-1 activity dependent on Kif4A low expression in breast cancer cells / 中国癌症杂志

ABSTRACT

Background and purpose:Chemotherapy is the important way of breast cancer treatment, but the drug-resistance has attracted special attention. The emergence of drug resistance is closely related to the abnormal enhancement of DNA-damage repair. Both Kif4A and PARP-1 are important molecules of DNA repair. The research investigated the function of Kif4A in epirubicin up-regulating the activity of PARP-1 in breast cancer cells and possible significance. Methods:Western blot was used to detect the expression of Kif4A and PARP-1 after treatment with epirubicin in MDA-MB-231 and MCF-7 cells; the expression of PARP-1 and its activity were detected after high expression of Kif4A and treatment with epirubicin;FCM was used to detect cell apoptosis after treatment with epirubicin combined with PARP-1 inhibitor 3-ABA. Results:Epirubicin up-regulated PARP-1 activity and induced low expression of Kif4A in breast cancer cells, both of them showed dose-dependent and time-dependent. After high expression of Kif4A, the activity of PARP-1 was inhibited and the apoptosis of cells increased, epirubicin partially reversed the activity of PARP-1 inhibited by high Kif4A expression. Both of epirubicin and 3-ABA induced cell apoptosis, combination of them further increased cell apoptosis compared with alone used (P<0.05). The results also showed the apoptosis rate of MDA-MB-231 cells induced by epirubicin, PARP-1 inhibitor 3-ABA and high expression Kif4A was higher than that of MCF-7 cells (P<0.05). Conclusion:Epirubicin increases the activity of PARP-1 dependent on the low expression of Kif4A in breast cancer cells. Kif4A might become a novel target for overcoming resistance of epirubicin.