Department of Food and Nutrition, Hannam University Daedeok Valley Campus, Daejeon 305-811, Korea.
Carcinogenesis. 2010 Jun;31(6):1092-9. doi: 10.1093/carcin/bgq040. Epub 2010 Feb 17.
Activation of the mammalian target of rapamycin (mTOR) pathway promotes tumorigenesis, and inhibiting the mammalian target of rapamycin complex 1 (mTORC1) has emerged as an attractive target for suppressing tumor growth. We found that selenium treatment of HT-29 colon cancer cells suppressed mTORC1 through Akt-independent and -dependent pathways. In Akt-independent mTORC1 inhibition in selenium-treated colon cancer cells, adenosine monophosphate-activated protein kinase (AMPK) alpha(1) was crucial for suppression of mTORC1 activity. In contrast, the Akt-dependent mTORC1 inhibition by selenium did not require AMPKalpha(1). The importance of the AMPKalpha(1)-mTORC1 pathway in mediating the antiproliferative action of selenium was examined in xenograft tumors, and the suppression of mTORC1 as well as Akt was concomitant with an increase in AMPKalpha(1) activity. These findings suggest that the antiproliferative effect of selenium is mediated by an Akt-independent AMPKalpha(1)/mTORC1 pathway or by the Akt/tuberous sclerosis complex 2 /mTORC1 pathway.
哺乳动物雷帕霉素靶蛋白（mTOR）途径的激活促进了肿瘤的发生，抑制哺乳动物雷帕霉素复合物 1（mTORC1）已成为抑制肿瘤生长的一个有吸引力的靶点。我们发现，硒处理 HT-29 结肠癌细胞通过 Akt 非依赖性和依赖性途径抑制 mTORC1。在硒处理的结肠癌细胞中，Akt 非依赖性 mTORC1 抑制中，腺苷一磷酸激活蛋白激酶（AMPK）α(1)对于抑制 mTORC1 活性至关重要。相比之下，硒对 mTORC1 的 Akt 依赖性抑制并不需要 AMPKα(1)。在异种移植肿瘤中，研究了 AMPKα(1)-mTORC1 途径在介导硒的抗增殖作用中的重要性，mTORC1 以及 Akt 的抑制伴随着 AMPKα(1)活性的增加。这些发现表明，硒的抗增殖作用是通过 Akt 非依赖性 AMPKα(1)/mTORC1 途径或 Akt/结节性硬化复合物 2/mTORC1 途径介导的。
