Department of Biomedical Sciences, University of Guelph, ON, Canada.
Cancer Lett. 2010 Nov 1;297(1):75-83. doi: 10.1016/j.canlet.2010.04.027. Epub 2010 May 26.
We examined the effect of hypoxia on apoptosis of human colorectal cancer (CRC) cells in vitro and in vivo. All cell lines tested were susceptible to hypoxia-induced apoptosis. DCA treatment caused significant apoptosis under normoxia in SW480 and Caco-2 cells, but these cells displayed decreased apoptosis when treated with DCA combined with hypoxia, possibly through HIF-1alpha dependent pathways. DCA treatment also induced significantly increased growth of SW480 tumor xenografts, and a decrease in TUNEL positive nuclei in hypoxic but not normoxic regions of treated tumors. Thus DCA is cytoprotective to some CRC cells under hypoxic conditions, highlighting the need for further investigation before DCA can be used as a reliable apoptosis-inducing agent in cancer therapy.
我们研究了缺氧对人结直肠癌细胞（CRC）体外和体内凋亡的影响。所有测试的细胞系都容易受到缺氧诱导的凋亡。在 SW480 和 Caco-2 细胞中，DCA 在常氧条件下导致明显的细胞凋亡，但这些细胞在与缺氧联合使用 DCA 时显示出凋亡减少，可能通过 HIF-1alpha 依赖途径。DCA 处理还显著诱导 SW480 肿瘤异种移植物的生长增加，并减少 TUNEL 阳性核在缺氧但不是常氧处理肿瘤区域。因此，DCA 在缺氧条件下对一些 CRC 细胞具有细胞保护作用，这突显了在 DCA 可作为癌症治疗中可靠的诱导凋亡剂之前，需要进一步研究。
