2. Academic Validation
  3. Genomic and tumor biological aspects of the anticancer nicotinamide phosphoribosyltransferase inhibitor FK866 in resistant human colorectal cancer cells

Genomic and tumor biological aspects of the anticancer nicotinamide phosphoribosyltransferase inhibitor FK866 in resistant human colorectal cancer cells

  • Genomics. 2019 Dec;111(6):1889-1895. doi: 10.1016/j.ygeno.2018.12.012.
Yoko Ogino 1,  Akira Sato 2,  Fumiaki Uchiumi 3,  Sei-Ichi Tanuma 4
Affiliations

Affiliations

  • 1 Department of Biochemistry, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Chiba 278-8510, Japan; Department of Gene Regulation, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Chiba 278-8510, Japan.
  • 2 Department of Biochemistry, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Chiba 278-8510, Japan. Electronic address: akirasat@rs.tus.ac.jp.
  • 3 Department of Gene Regulation, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Chiba 278-8510, Japan.
  • 4 Department of Biochemistry, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Chiba 278-8510, Japan; Department of Genomic Medicinal Science, Research Institute for Science and Technology, Organization for Research Advancement, Tokyo University of Science, Noda, Chiba 278-8510, Japan.
PMID: 30582964 DOI: 10.1016/j.ygeno.2018.12.012
Abstract

Cancer cells' resistance to drugs remains an important problem affecting Cancer treatment strategies. We previously studied the nicotinamide phosphoribosyltransferase (NAMPT) inhibitor FK866's resistance mechanisms in the human colorectal Cancer HCT116 cells. We established an acquired FK866-resistant cell line, HCT116RFK866. In this study, we investigated gene mutations in parental HCT116 and HCT116RFK866 cells using exome Sequencing technology. The results indicated cluster genes related to NAD+ biosynthesis (including NAMPT), DNA repair, and ATP-binding cassette transporters were differentially altered in these cells. Interestingly, HCT116RFK866 cells, which are resistant to Other class NAMPT inhibitors, were more sensitive to the Anticancer 5-fluorouracil and cisplatin and γ-ray irradiation compared to parental HCT116 cells. This higher sensitivity appears to cause a genetic change in the identified gene clusters by resistance to the NAMPT Inhibitor FK866. Collectively, these novel findings provide a better understanding of Anticancer candidate NAMPT inhibitors with regard to resistance mechanisms and Cancer chemotherapy strategies.

Keywords

ABC transporter; Drug resistance; FK866; NAD(+) biosynthetic pathway; NAMPT; NAMPT inhibitor.

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