@Article{096504016X14587366983838,
AUTHOR = {Pei Yin, Jinpeng Jia, Jijun Li, Yan Song, Yiyan Zhang, Fengkun Chen},
TITLE = {ABT-737, a Bcl-2 Selective Inhibitor, and Chloroquine Synergistically Kill Renal Cancer Cells},
JOURNAL = {Oncology Research},
VOLUME = {24},
YEAR = {2016},
NUMBER = {1},
PAGES = {65--72},
URL = {http://www.techscience.com/or/v24n1/56611},
ISSN = {1555-3906},
ABSTRACT = {Renal cell carcinoma (RCC) is the most common malignancy in the kidney in the world, and the 5-year overall survival for patients remains poor due to the lack of effective treatment strategies. Although ABT-737, as 
a Bcl-2/Bcl-xL inhibitor, has recently emerged as a novel cancer therapeutic reagent, apoptosis induced by 
ABT-737 is often blocked in several types of cancer cells. This study investigated whether the combination of 
the small-molecule BH3 mimetic ABT-737 and the lysosome inhibitor chloroquine was an effective strategy 
for treating renal cancer cells. We found that the combination of ABT-737 and chloroquine synergistically 
decreased cell viability when compared to treatment with either single reagent. Cell apoptosis induced by a 
combined treatment was markedly inhibited by the caspase inhibitors z-DEVD-FMK and z-VAD-FMK. It 
was also inhibited by cathepsin inhibitor E-64 and CTSI (cathepsin inhibitor), which suggested that apoptosis 
was dependent on the cascade of caspase activation and cathepsins released from lysosomes. Furthermore, we 
found that ABT-737 could increase the cell level of ROS, which triggers cathepsin-mediated cell death and augments the role of chloroquine in cell death. So the combination of ABT-737 and chloroquine was an effective 
strategy for the treatment of renal cancer cells, and this combined strategy may widen the therapeutic window 
of ABT-737 and chloroquine as well as enhance the clinical efficacy of synergistic drug combinations.},
DOI = {10.3727/096504016X14587366983838}
}