Regulative Effect of Nampt on Tumor Progression and Cell Viability in Human Colorectal Cancer

Abstract

Colorectal cancer (CRC) is the third most common cancer disease. Here we examined Nampt expression in patients with CRC and the effect of Nampt on cell viability in CRC cells. Nampt protein was overexpressed in colorectal adenoma as well as colorectal carcinoma. The immunoreactive staining of Nampt was negative in the adjacent normal colorectal tissue, weak in colorectal adenoma, and strong in colorectal carcinoma, which may represent tumor progression. Further evaluation of clinical data showed that Nampt expression was not correlated with the clinicopathological characteristics of CRC. Additionally, our in vitro studies demonstrated that Nampt promotes CRC cell viability, whereas the Nampt inhibitor FK866 suppressed CRC cell viability, which was in concordance with the previous studies in other cancer cells. Treatment with Nampt-siRNA reduced the Nampt protein expression resulting in the inhibition of the cell viability of HCT116 and Caco2. Thus, the involvement of Nampt in cell growth indicates that Nampt may play an important role in colorectal tumorigenesis. As a consequence, our results suggest that Nampt may be considered as a progression marker of colorectal tumor and a potentially therapeutic target for the treatment of CRC.

Targeting c-MYC through Interference with NAMPT and SIRT1 and Their Association to Oncogenic Drivers in Murine Serrated Intestinal Tumorigenesis

“…These data together with our previous study [14] indicate, that NAMPT and SIRT1 may represent therapeutic targets in serrated B-Raf or Kras-driven, and also in WNT pathway driven colorectal cancers [46], [64], [65]. Future studies using preclinical models will have to address whether higher vulnerabilities of BRAF -mutant cell lines observed in vitro translates to similar findings in vivo.…”

A Negative Feedback Loop Between NAMPT and TGF-β Signaling Pathway in Colorectal Cancer Cells

“…Similarly, the results of immunohistochemical staining from previous studies indicated that high expression of NAMPT in CRC is correlated with invasion, advanced TNM stage, and short overall survival. 6 , 8 Nevertheless, the underlying regulatory mechanisms of NAMPT in CRC are still limited. NAMPT is a potent oncogene that modulates cancer stem cell properties through Sirt1 and PARP in CRC.…”

“… 6 , 7 Our previous study has shown that NAMPT as a potential progression marker of CRC promotes CRC cell viability. 8 In addition to its effect on impairment of cellular energy metabolism in cancer cells, NAMPT is also involved in non-metabolic functions such as sirtuin function, DNA repair machinery, redox homeostasis, and tumor-related immune suppression. 9 It has been shown that NAMPT is a molecular target of potent anticancer agents and its inhibitors have been applied in several early phase clinical trials for cancer therapy.…”

The sensitivity of adipose tissue visfatin mRNA expression to lipopolysaccharide-induced endotoxemia is increased by ovariectomy in female rats

“…Each piece was transferred into 12-well plate filled with 2 mL medium (DMEN/F-12 (1:1) with L-glutamine and 15 mM HEPES, antibiotics, and 10% fetal bovine serum), and incubated at 37°C, 90% humidity, and 5% CO2 for 24 h. Thereafter the medium was removed and replaced by 2 mL fresh medium (control), medium with 500 ng/mL LPS (LPS), medium with 500 ng/mL LPS and visfatin antagonist FK-866 (LPS + FK-866 10 nM, LPS + FK-866,100 nM, or LPS + FK-866,500 nM) (Funakoshi, Tokyo, Japan) and incubated for 24 h. The mRNA expression levels of IL-1β, IL-6, and TNF-α were quantified in cultured WAT. These doses of FK-866 were used in previous reports [20][21][22].…”