title: NECTIN-4 increased the 5-FU resistance in colon cancer cells by inducing the PI3K-AKT cascade.
abstract: OBJECTIVE
  5-Fluorouracil is the most commonly used drug for the treatment of colon cancer, yet clinical resistance to this drug is frequently observed in patients making this drug ineffective. Thus, identification of gene responsible for 5-FU resistance is of utmost importance.
  
  
  METHODS
  Cellular cytotoxicity and expressions of different protein markers in colon cancer cells were measured by MTT assay and Western blotting, respectively. Cell cycle regulation, migration and colony formation ability were measured by FACS, wound-healing assay and clonogenic assay, respectively.
  
  
  RESULTS
  Increased NECTIN-4 expression was observed in 5-FU-resistant (5-FU-R) and 5-FU-exposed HCT-116 cells. A significant increase in the cell proliferation, migration, colony formation, and resistant to 5-FU were noted in 5-FU-R cells, but reverse was observed after silencing of NECTIN-4. Apoptosis caused by 5-FU in 5-FU-R cells after NECTIN-4 knockdown indicates that NECTIN-4 is responsible for 5-FU resistance. Cell survival proteins were upregulated in 5-FU-R and NECTIN-4-over-expressed cells and downregulated in NECTIN-4 knockdown or LY294002-pretreated 5-FU-R cells. Drug combination of BCNU + Resveratrol decreased the cell survival and NECTIN-4 expressions in 5-FU-R cells and NECTIN-4-over-expressed cells.
  
  
  CONCLUSIONS
  Our data suggest that NECTIN-4 is responsible for 5-FU resistance and BCNU + Resveratrol combination can be used to increase the 5-FU sensitivity.
authors.affiliation: KIIT School of Biotechnology, KIIT University, Campus-11, Patia, Bhubaneswar, 751024, Orissa, India.
authors.forename: Dipon
authors.initials: D
authors.lastname: Das
authors.forename: Shakti Ranjan
authors.initials: SR
authors.lastname: Satapathy
authors.forename: Sumit
authors.initials: S
authors.lastname: Siddharth
authors.forename: Anmada
authors.initials: A
authors.lastname: Nayak
authors.forename: Chanakya Nath
authors.initials: CN
authors.lastname: Kundu
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000235:genetics; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D005472:Fluorouracil / Q000494:pharmacology*; D045325:HCT116 Cells; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction; D014162:Transfection; D000075983:Nectins
chemical_list: D000964:Antimetabolites, Antineoplastic; D015815:Cell Adhesion Molecules; D005472:Fluorouracil; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C442228:NECTIN4 protein, human; D000075983:Nectins