DNA-PK inhibitors and anti-apoptotic proteins inhibitors have individually been used to sensitise cancer cells to chemotherapy drugs. NU7026 has been demonstrated to be a potent, specific inhibitor of DNA-PK, and thus inhibits DNA DSB repair. While, ABT-737 inhibits anti-apoptotic members of the bcl-2 family (bcl-2, bcl-xl and bcl-w), and thus induces apoptosis. These inhibitors have been used singularly in combination with doxorubicin to sensitise cells to the effects of doxorubicin on T47D breast cancer cells. But the combined effect of inhibiting repair, and promoting apoptosis following treatment with doxorubicin has yet to be explored, and was the focus of the current study. To determine the impact of this combination, a series of experiments to determine changes in cell number, cell cycle arrest, DNA damage and apoptosis was conducted, followed by molecular studies to determine the apoptotic pathway/s that may be involved.
The 'triple' combination did not improve the efficacy of doxorubicin treatment. It appears that the effects of NU7026 and ABT-737 are acting through similar pathways, and when used in combination block any beneficial effect