The multikinase inhibitor sorafenib induces caspase-dependent apoptosis in PC-3 prostate cancer cells

被引：13
作者：
Huang, Rui [3 ]
Chen, Xue-Qin [2 ]
Huang, Ying [2 ]
Chen, Ni [2 ]
Zeng, Hao [1 ]
机构：
[1] Sichuan Univ, Dept Urol, W China Hosp, Chengdu 610041, Peoples R China
[2] Sichuan Univ, Pathol Lab, State Key Lab Biotherapy, W China Hosp, Chengdu 610041, Peoples R China
[3] Sichuan Univ, Dept Nucl Med, Natl Key Discipline Med Imaging & Nucl Med, W China Hosp, Chengdu 610041, Peoples R China
来源：
ASIAN JOURNAL OF ANDROLOGY | 2010年 / 12卷 / 04期
基金：
中国国家自然科学基金;
关键词：
apoptosis; PC-3 prostate cancer cells; prostate cancer; sorafenib; DOWN-REGULATION; PHASE-II; RAF/MEK/ERK PATHWAY; FACTOR AIF; BCL-X; SURVIVIN; MCL-1; BAY-43-9006; KINASE; GROWTH;
D O I：
10.1038/aja.2010.21
中图分类号：
R69 [泌尿科学（泌尿生殖系疾病）];
学科分类号：
摘要：
The present study investigated the effects of the multikinase inhibitor sorafenib on androgen-independent cancer cells viability and intracellular signaling. Human androgen-independent PC-3 prostate cancer cells were treated with sorafenib. At concentration that suppresses extracellular signal-regulated kinase phosphorylation, sorafenib treatment reduced the mitochondrial transmembrane potential. Sorafenib also down-modulated the levels of myeloid cell leukemia 1, survivin and cellular inhibitor of apoptosis protein 2. Sorafenib induced caspase-3 cleavage and the mitochondrial release of cytochrome c. However, no nuclear translocation of apoptosis inducing factor was detected after treatment and the pan-caspase inhibitor Z-VAD-FMK had an obvious protective effect against the drug. In conclusion, sorafenib induces apoptosis through a caspase-dependent mechanism with down-regulated antiapoptotic proteins in androgen-independent prostate cancer cells in vitro.
引用
收藏
页码：527 / 534
页数：8
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