Ambs S, Merriam W G, Ogunfusika M O, Bennett W P, Ishibe N, Hussain S P, Tzeng E E, Geller D A, Billiar T R, Harris C C
Laboratory of Human Carcinogenesis, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA.
Nat Med. 1998 Dec;4(12):1371-6. doi: 10.1038/3957.
The finding of frequent nitric oxide synthase expression in human cancers indicates that nitric oxide has a pathophysiological role in carcinogenesis. To determine the role of nitric oxide in tumor progression, we generated human carcinoma cell lines that produced nitric oxide constitutively. Cancer cells expressing inducible nitric oxide synthase that had wild-type p53 had reduced tumor growth in athymic nude mice, whereas those with mutated p53 had accelerated tumor growth associated with increased vascular endothelial growth factor expression and neovascularization. Our data indicate that tumor-associated nitric oxide production may promote cancer progression by providing a selective growth advantage to tumor cells with mutant p53, and that inhibitors of inducible nitric oxide synthase may have therapeutic activity in these tumors.
在人类癌症中频繁发现一氧化氮合酶表达，这表明一氧化氮在致癌过程中具有病理生理作用。为了确定一氧化氮在肿瘤进展中的作用，我们构建了组成型产生一氧化氮的人癌细胞系。表达诱导型一氧化氮合酶且具有野生型p53的癌细胞在无胸腺裸鼠中的肿瘤生长减缓，而那些p53发生突变的癌细胞则肿瘤生长加速，这与血管内皮生长因子表达增加和新血管形成有关。我们的数据表明，肿瘤相关的一氧化氮产生可能通过为具有突变p53的肿瘤细胞提供选择性生长优势来促进癌症进展，并且诱导型一氧化氮合酶抑制剂可能对这些肿瘤具有治疗活性。
