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首页> 外文期刊>Canadian Journal of Physiology and Pharmacology >Role of nitric oxide in tumour progression with special reference to a murine breast cancer model.
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Role of nitric oxide in tumour progression with special reference to a murine breast cancer model.

机译：一氧化氮在肿瘤进展中的作用，特别参考鼠类乳腺癌模型。

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摘要

Nitric oxide (NO) is a potent bioactive molecule produced in the presence of NO synthase (NOS) enzymes, which mediates numerous physiological functions under constitutive conditions. Sustained overproduction of NO (and NO-reaction products), typically under inductive conditions, can lead to cell cycle arrest and cellular apoptosis. Furthermore, carcinogenesis may result from mutational events following NO-mediated DNA damage and hindrance to DNA repair (e.g., mutation of tumour-suppressor gene p53). In a majority of human and experimental tumours, tumour-derived NO appears to stimulate tumour progression; however, for a minority of tumours, the opposite has been reported. This apparent discrepancy may be explained by differential susceptibility of tumour cells to NO-mediated cytostasis or apoptosis, and the emergence of NO-resistant and NO-dependent clones. NO-resistance may be mediated by p53 inactivation, and upregulation of cyclo-oxygenase-2 and heat shock protein 70 (HSP70). In a murine mammary tumour model, tumour-derived NO promoted tumour growth and metastasis by enhancing invasive, angiogenic, and migratory capacities of tumour cells. Invasion stimulation followed the altered balance of matrix metalloproteases and their inhibitors; migration stimulation followed activation of guanylate cyclase and MAP kinase pathways. Selective NOS inhibitors may have a therapeutic role in certain cancers.
机译：一氧化氮（NO）是在NO合酶（NOS）酶存在下产生的有效生物活性分子，该酶在组成条件下介导许多生理功能。通常在诱导条件下持续过量生产NO（和NO反应产物）会导致细胞周期停滞和细胞凋亡。此外，癌变可能是由NO介导的DNA损伤和DNA修复障碍（例如，肿瘤抑制基因p53的突变）后的突变事件引起的。在大多数人类和实验性肿瘤中，源自肿瘤的一氧化氮似乎会刺激肿瘤的进展。然而，对于少数肿瘤，已经报道了相反的结果。这种明显的差异可能是由于肿瘤细胞对NO介导的细胞停滞或凋亡的敏感性不同，以及NO耐药和NO依赖性克隆的出现。 NO耐药性可能是由p53失活，环加氧酶2和热休克蛋白70（HSP70）上调所介导的。在鼠类乳腺肿瘤模型中，肿瘤源性NO通过增强肿瘤细胞的侵袭，血管生成和迁移能力来促进肿瘤生长和转移。侵袭刺激是由于基质金属蛋白酶及其抑制剂的平衡改变所致。迁移刺激跟随鸟苷酸环化酶和MAP激酶途径的激活。选择性NOS抑制剂可能在某些癌症中具有治疗作用。

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