Wang Feng, Zhang Ruixue, Xia Tian, Hsu Erin, Cai Ying, Gu Zhennan, Hankinson Oliver
Department of Pathology and Laboratory Medicine, Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA 90095, USA.
Cancer Lett. 2007 Nov 18;257(2):274-82. doi: 10.1016/j.canlet.2007.08.001. Epub 2007 Sep 14.
Hypoxia increased the ability of two human cancer cell lines, PC-3M and T24, to invade through Matrigel, while sodium nitroprusside (SNP), a nitric oxide (NO) donor, strongly inhibited this invasion, along with down-regulating HIF-1alpha. SNP also inhibited the function of mitochondria in PC-3M cells, and mitochondrion-specific inhibitors reduced the invasion of these cells. Furthermore, knocking down either Rieske iron-sulfur protein (Fe-S) of mitochondrial complex III or HIF-1beta in these cells decreased their invasive potential. Our findings suggest that NO inhibits invasion of cancer cells via both inhibition of HIF-1, and impairment of mitochondria.
缺氧增强了两种人类癌细胞系PC - 3M和T24通过基质胶侵袭的能力，而一氧化氮（NO）供体硝普钠（SNP）强烈抑制这种侵袭，同时下调缺氧诱导因子-1α（HIF - 1α）。SNP还抑制了PC - 3M细胞中线粒体的功能，线粒体特异性抑制剂降低了这些细胞的侵袭能力。此外，敲低这些细胞中线粒体复合物III的 Rieske铁硫蛋白（Fe - S）或HIF - 1β会降低它们的侵袭潜力。我们的研究结果表明，NO通过抑制HIF - 1和损害线粒体来抑制癌细胞的侵袭。
