Author/Authors :
Zheng، نويسنده , , Lin and Yang، نويسنده , , Wei and Zhang، نويسنده , , Chong and Ding، نويسنده , , Wan-jing and Zhu، نويسنده , , Hong and Lin، نويسنده , , Neng-ming and Wu، نويسنده , , Hong-hai and He، نويسنده , , Qiaojun and Yang، نويسنده , , Bo، نويسنده ,
Abstract :
The present study showed that GDC-0941 potently sensitized breast cancer to ABT-737 in vitro and in vivo. ABT-737 exhibited limited lethality in breast cancer cells; however, when combined with GDC-0941, it displayed strong synergistic cytotoxicity and enhanced caspase-mediated apoptosis. GDC-0941 promoted proteasomal degradation of Mcl-1, of which the overexpression has been validated to confer ABT-737 resistance, thereby enhanced the anticancer efficacy of ABT-737. Furthermore, the combination of GDC-0941 and ABT-737 exerted increased anti-tumor efficacy on MDA-MB-231 xenograft models. Overall, our data described unprecedentedly the promising therapeutic potential and underlying mechanisms of combining GDC-0941 with ABT-737 in treating breast cancer.
Keywords :
GDC-0941 , synergism , ABT-737 , apoptosis , Mcl-1
