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Nicotinamide phosphoribosyltransferase (NAMPT) possesses various functions in human cells, and altered NAMPT expression is associated with human carcinogenesis. The present study detected the expression of NAMPT in normal and cancerous breast tissues from 83 patients using immunohistochemistry, and analyzed its association with the clinicopathological and survival data of the patients. NAMPT was significantly overexpressed in the breast invasive ductal carcinoma tissues compared with adjacent normal mammary gland tissues. Upregulated NAMPT expression was associated with a larger tumor size, lymph node metastasis, advanced clinical tumor-node-metastasis stages, and estrogen receptor and progesterone receptor expression. Furthermore, NAMPT expression was associated with poor overall and disease-free survival in patients with breast cancer. In conclusion, NAMPT increased protein expression in tumor cells may contribute to the development and progression of breast invasive ductal carcinoma. Thus, detection of NAMPT expression might be useful as a biomarker for the early detection and prognosis prediction of breast cancer.

Objectives: To study the expression of nicotinamide phosphoribosyl transferase (Nampt) and vascular endothelial growth factor-A (VEGF-A) in gastric carcinoma and investigate their correlations to clinicopathologic features and prognostic significance., Methods: The proteins of Nampt and VEGF-A in 68 specimens of gastric carcinoma and 59 specimens normal gastric tissue were detected by immunohistochemistry during January 2000 to December 2004, and the 68 patients were followed up., Results: Nampt protein was detected in the cytoplasm of both tissues, and Nampt in gastric carcinoma (13 ± 5) were significantly higher than that in normal gastric tissue (6 ± 3) (t = 7.46, P < 0.01). The expression of Nampt was correlated to invasive depth (F = 4.693, P = 0.034), lymph node metastasis (F = 4.027, P = 0.049), clinical TNM stage (F = 9.979, P = 0.002), but not to gender, age, tumor location, tumor size, differentiation (P > 0.05). The expression of Nampt is correlated with survival of patients that underwent surgical resection for gastric cancer. The survival rate of patients in negative of Nampt was very higher than that of the positive patients, and its co-expression with VEGF-A showed a trend towards poorer survival. The positive correlation was found between the expression of Nampt and VEGF-A in gastric carcinoma (r = 0.293, P = 0.015)., Conclusions: The expression of Nampt is positively correlated to that of VEGF-A in gastric carcinoma. The correlation between the expression of Nampt and VEGF-A in gastric carcinoma plays an important role cooperatively in carcinogenesis, development and metastasis of gastric carcinoma.

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.

Nampt/PBEF/visfatin is the rate-limiting enzyme that catalyzes the first step in NAD biosynthesis from nicotinamide and regulates growth, apoptosis and angiogenesis of mammalian cells. This enzyme was originally cloned as a putative cytokine shown to enhance the B cell precursor maturation in the presence of IL-7 and stem cell factor. A number of cancers have increased expression of Nampt/PBEF/visfatin, which regulates a variety of different signaling pathways such as PI3K/Akt, ERK1/2 and STAT3. FK866/APO866 and CHS828/GMX1777 are two known inhibitors of Nampt/PBEF/visfatin and have been evaluated as anticancer agents in the clinic. This review will focus on its role in carcinogenesis and cancer progression and its inhibitors as therapeutic target for cancer treatment.