Girotti Albert W
Department of Biochemistry, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Cancers (Basel). 2016 Oct 20;8(10):96. doi: 10.3390/cancers8100096.
Nitric oxide (NO) produced by nitric oxide synthase (NOS) enzymes is a free radical molecule involved in a wide variety of normophysiologic and pathophysiologic processes. Included in the latter category are cancer promotion, progression, and resistance to therapeutic intervention. Animal tumor photodynamic therapy (PDT) studies several years ago revealed that endogenous NO can reduce PDT efficacy and that NOS inhibitors can alleviate this. Until relatively recently, little else was known about this anti-PDT effect of NO, including: (a) the underlying mechanisms; (b) type(s) of NOS involved; and (c) whether active NO was generated in vascular cells, tumor cells, or both. In addressing these questions for various cancer cell lines exposed to PDT-like conditions, the author's group has made several novel findings, including: (i) exogenous NO can scavenge lipid-derived free radicals arising from photostress, thereby protecting cells from membrane-damaging chain peroxidation; (ii) cancer cells can upregulate inducible NOS (iNOS) after a PDT-like challenge and the resulting NO can signal for resistance to photokilling; (iii) photostress-surviving cells with elevated iNOS/NO proliferate and migrate/invade more aggressively; and (iv) NO produced by photostress-targeted cells can induce greater aggressiveness in non-targeted bystander cells. In this article, the author briefly discusses these various means by which NO can interfere with PDT and how this may be mitigated by use of NOS inhibitors as PDT adjuvants.
一氧化氮合酶（NOS）产生的一氧化氮（NO）是一种自由基分子，参与多种正常生理和病理生理过程。后者包括癌症的促进、进展以及对治疗干预的抵抗。几年前的动物肿瘤光动力疗法（PDT）研究表明，内源性NO会降低PDT疗效，而NOS抑制剂可以缓解这种情况。直到最近，关于NO的这种抗PDT作用，人们所知甚少，包括：（a）潜在机制；（b）涉及的NOS类型；以及（c）活性NO是在血管细胞、肿瘤细胞还是两者中产生。在针对暴露于类似PDT条件的各种癌细胞系解决这些问题时，作者团队有了一些新发现，包括：（i）外源性NO可以清除光应激产生的脂质衍生自由基，从而保护细胞免受膜损伤性链式过氧化的影响；（ii）癌细胞在类似PDT的刺激后可以上调诱导型NOS（iNOS），产生的NO可以发出抗光杀伤的信号；（iii）iNOS/NO升高的光应激存活细胞增殖并更积极地迁移/侵袭；以及（iv）光应激靶向细胞产生的NO可以诱导非靶向旁观者细胞产生更大的侵袭性。在本文中，作者简要讨论了NO干扰PDT的各种方式，以及如何通过使用NOS抑制剂作为PDT佐剂来减轻这种干扰。
