mTORC2型
蛋白激酶B
PI3K/AKT/mTOR通路
芦荟大黄素
癌症研究
PTEN公司
前列腺癌
大黄素
化学
细胞生长
生物
细胞生物学
mTORC1型
癌症
生物化学
磷酸化
信号转导
医学
内科学
作者
Kangdong Liu,Chanmi Park,Shengqing Li,Ki Won Lee,Haidan Liu,Long He,Nak-Kyun Soung,Jong Seog Ahn,Ann M. Bode,Ziming Dong,Bo Yeon Kim,Zigang Dong
出处
期刊:Carcinogenesis
[Oxford University Press]
日期:2012-04-24
卷期号:33 (7): 1406-1411
被引量:47
标识
DOI:10.1093/carcin/bgs156
摘要
Phosphatidylinositol 3-kinase (PI3-K) amplification and phosphatase and tensin homolog (PTEN) deletion-caused Akt activation contribute to the development of prostate cancer. Mammalian target of rapamycin complex 2 (mTORC2) is a kinase complex comprised of mTOR, Rictor, mSin1, mLST8/GβL and PRR5 and functions in the phosphorylation of Akt at Ser473. Herein, we report that mTORC2 plays an important role in PC3 androgen refractory prostate cell proliferation and anchorage-independent growth. Aloe-emodin, a natural compound found in aloe, inhibited both proliferation and anchorage-independent growth of PC3 cells. Protein content analysis suggested that activation of the downstream substrates of mTORC2, Akt and PKCα, was inhibited by aloe-emodin treatment. Pull-down assay and in vitro kinase assay results indicated that aloe-emodin could bind with mTORC2 in cells and inhibit its kinase activity. Aloe-emodin also exhibited tumor suppression effects in vivo in an athymic nude mouse model. Collectively, our data suggest that mTORC2 plays an important role in prostate cancer development and aloe-emodin suppresses prostate cancer progression by targeting mTORC2.
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