Department of Medicine, University of Illinois at Chicago, Chicago, IL, USA.
Cell Cycle. 2011 Oct 1;10(19):3269-73. doi: 10.4161/cc.10.19.17735.
Apoptosis has been widely accepted as the primary mechanism of drug-induced cell death. Recently, a second type of cell death pathway has been demonstrated: autophagy, also called programmed type II cell death. Autophagy is a highly regulated process, by which selected components of a cell are degraded. It primarily functions as a cell survival mechanism under stress. However, persistent stress can also promote extensive autophagy leading to cell death. Forkhead box M1 (FoxM1), an oncogenic transcription factor that is abundantly expressed in a wide range of human cancers. Here we evaluated the role of FoxM1 in sensitivity of human cancer cells to proteasome inhibitor-induced apoptosis and autophagy. We found that FoxM1 knockdown sensitized the human cancer cells to apoptotic cell death induced by proteasome inhibitors, such as, MG132, bortezomib and thiostrepton, while it did not affect the levels of autophagy following treatment with these drugs.
细胞凋亡已被广泛认为是药物诱导细胞死亡的主要机制。最近，已经证明了第二种细胞死亡途径：自噬，也称为程序性细胞死亡 II 型。自噬是一种高度调节的过程，通过该过程，细胞的某些选定成分被降解。它主要作为应激下的细胞存活机制发挥作用。然而，持续的应激也可以促进广泛的自噬导致细胞死亡。叉头框 M1（FoxM1）是一种癌基因转录因子，在广泛的人类癌症中大量表达。在这里，我们评估了 FoxM1 在人癌细胞对蛋白酶体抑制剂诱导的细胞凋亡和自噬敏感性中的作用。我们发现，FoxM1 敲低使人类癌细胞对蛋白酶体抑制剂（如 MG132、硼替佐米和噻唑嗪）诱导的细胞凋亡敏感，而对这些药物处理后自噬水平没有影响。
