Role of nitric oxide in carcinogenesis and tumour progression

被引:513
|
作者
Lala, Peeyush K. [1 ,2 ,3 ]
Chakraborty, Chandan [1 ,2 ,3 ]
机构
[1] Univ Western Ontario, Dept Anat & Cell Biol, London, ON N6A 5C1, Canada
[2] Univ Western Ontario, Dept Oncol, London, ON, Canada
[3] Univ Western Ontario, Dept Pathol, London, ON, Canada
来源
LANCET ONCOLOGY | 2001年 / 2卷 / 03期
关键词
D O I
10.1016/S1470-2045(00)00256-4
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Nitric oxide (NO) is a short-lived molecule required for many physiological functions, produced from L-arginine by NO synthases (NOS). It is a free radical, producing many reactive intermediates that account for its bioactivity. Sustained induction of the inducible form of NOS (iNOS) in chronic inflammation may be mutagenic, through NO-mediated DNA damage or hindrance to DNA repair, and thus potentially carcinogenic. Expression of iNOS is positively associated with P53 mutation in tumours of the colon, lung, and oropharynx. Progression of a large majority of human and experimental tumours seems to be stimulated by NO resulting from activation of iNOS or constitutive NOS, whereas inhibition is documented in others. This discrepancy is largely explained by differential sensitivity of tumour cells to NO-mediated cytostasis or apoptosis and clonal evolution of NO-resistant and NO-dependent cells. P53 mutation or loss is one of many events linked with NO resistance and dependence. NO can stimulate tumour growth and metastasis by promoting migratory, invasive, and angiogenic abilities of tumour cells, which may also be triggered by activation of cyclo-oxygenase (COX) -2. Thus, selective inhibitors of NOS, COX, or both may have a therapeutic role in certain cancers.
引用
收藏
页码:149 / 156
页数:8
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