Department of General Surgery, First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an 710061, PR China.
Oncol Rep. 2011 Nov;26(5):1251-7. doi: 10.3892/or.2011.1378. Epub 2011 Jul 4.
Nicotinamide phosphoribosyltransferase (Nampt), an enzyme involved in the NAD⁺ salvage pathway, is over-expressed and important in the carcinogenesis in several types of cancers. The expression of Nampt and its role in gastric cancer remain largely unknown. In this study, using real-time PCR and Western blotting we found that Nampt was overexpressed at the mRNA and protein levels, respectively, in established gastric cancer cells and human gastric cancer tissues. The specific Nampt inhibitor FK866 repressed gastric cancer cell proliferation, as assessed by MTT assay. Using transwell and soft agar clonogenic assays, we also found that FK866 suppressed gastric cancer cell migration and anchorage-independent growth, respectively. These inhibitory effects of FK866 were accompanied by significantly decreased expression of VEGF, MMP2, MMP9 and NF-κB. As determined by MTT assay and flow cytometry, FK866 also increased the chemo-sensitivity of gastric cancer cells to fluorouracil by greater inhibition of cell proliferation and the induction of apoptosis. Our findings indicate that Nampt may be a new therapeutic target for gastric cancer.
烟酰胺磷酸核糖转移酶（Nampt）是参与 NAD⁺补救途径的一种酶，在几种类型的癌症的致癌作用中过度表达且非常重要。Nampt 的表达及其在胃癌中的作用在很大程度上仍然未知。在这项研究中，我们使用实时 PCR 和 Western blot 发现，Nampt 在已建立的胃癌细胞和人胃癌组织中的 mRNA 和蛋白水平上分别过表达。特异性的 Nampt 抑制剂 FK866 通过 MTT 测定评估抑制了胃癌细胞的增殖。通过 Transwell 和软琼脂集落形成测定，我们还发现 FK866 分别抑制了胃癌细胞的迁移和锚定非依赖性生长。FK866 的这些抑制作用伴随着 VEGF、MMP2、MMP9 和 NF-κB 的表达显著降低。通过 MTT 测定和流式细胞术确定，FK866 通过更抑制细胞增殖和诱导细胞凋亡，也增加了胃癌细胞对氟尿嘧啶的化疗敏感性。我们的研究结果表明，Nampt 可能是胃癌的一个新的治疗靶点。
