FK866 inhibits the epithelial‑mesenchymal transition of hepatocarcinoma MHCC97‑H cells

Zhang,Bin; Shi,Dongmei; Zhang,Xiangyu; Liang,Guanzhao; Liu,Weida; Qiao,Sen

doi:10.3892/ol.2018.9541

FK866 inhibits the epithelial‑mesenchymal transition of hepatocarcinoma MHCC97‑H cells

Authors:
- Bin Zhang
- Dongmei Shi
- Xiangyu Zhang
- Guanzhao Liang
- Weida Liu
- Sen Qiao
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Affiliations: School of Medicine and Life Sciences, University of Jinan‑Shandong Academy of Medical Sciences, Jinan, Shandong 250062, P.R. China, Department of Dermatology, Jining No. 1 People's Hospital, Jining, Shandong 272011, P.R. China, Department of Pathology, Jining No. 1 People's Hospital, Jining, Shandong 272011, P.R. China, Department of Mycology, Institute of Dermatology, Chinese Academy of Medical Sciences, Peking Union Medical College, Nanjing, Jiangsu 210042, P.R. China, Department of Hepatobiliary Surgery, Jining No. 1 People's Hospital, Jining, Shandong 272011, P.R. China
Published online on: October 3, 2018 https://doi.org/10.3892/ol.2018.9541
Pages: 7231-7238
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Epithelial‑mesenchymal transition (EMT) is known to serve a pivotal function in hepatocellular carcinoma (HCC) metastasis. Nicotinamide phosphoribosyltransferase (NAMPT), the key enzyme in the nicotinamide‑adenine dinucleotide (NAD+)‑mediated pathway for the activation of silent information regulator 1 (SIRT1), serves a key function in HCC cell invasion and metastasis. Previous studies demonstrated that FK866, a targeted NAMPT inhibitor, inhibits the viability of HCC cells and induces cancer cell apoptosis; however, the effect of FK866 on the invasion and metastasis of HCC cells, particularly those associated with EMT through the SIRT1 pathway, remains unknown. In the present study, FK866 was identified to inhibit the capability of invasion and metastasis of cells from the HCC MHCC97‑H line in a dose‑dependent manner using a wound healing assay, an invasion assay and a migration assay. Furthermore, FK866 markedly decreased NAD+ and adenosine 5'‑triphosphate content in MHCC97‑H cells by inhibiting NAMPT expression. The results of the present study also revealed that FK866 led to a decrease in the expression of SIRT1, and to increased and decreased levels of the EMT marker proteins epithelial cadherin and vimentin, respectively, in MHCC97‑H cells. Furthermore, FK866 inhibited the SIRT1‑mediated EMT, invasion and migration of HCC cells by decreasing the expression of the NAMPT/NAD+ pathway. Taken together, the results of the present study suggest that FK866 may be an effective drug targeting HCC metastasis and invasion, and that the NAMPT/NAD+/SIRT1 pathway may be a potential therapeutic target for HCC.

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