title: The cytotoxic effect of GW843682X on nasopharyngeal carcinoma.
abstract: GW843682X is a publicly available anti-cancer compound by inhibiting Polo-like kinase. Previous studies revealed that GW843682X inhibited the proliferation of various tumor cell lines. In this study, the cytotoxic effect of GW843682X was investigated on cell proliferation, cell cycle and apoptosis of nasopharyngeal carcinoma 5-8F cells.
  
  
  
  Cell morphological changes were observed by inverted microscopy. Cell proliferation was tested by CCK8 assay. Cell cycle arrest and apoptosis were tested by flow cytometry. The mechanism of apoptosis was investigated by RT-PCR to determine the mRNA expression of IAP-1, IAP-2, XIAP, and survivin.
  
  
  
  GW843682X resulted in remarkable cell morphological changes with the increase of drug concentrations. CCK8 assay revealed that GW843682X inhibited the proliferation and induced apoptosis of 5-8F cells in a dose-dependent manner (IC50=62.5-125nmol/L). After treating 5-8F cells with different doses of GW843682X for 12 h, G2/M phase cells significantly increased while G0/G1 phase cells remarkably decreased. Interestingly, GW843682X signiﬁcantly inhibited the mRNA expression of IAP-1 and survivin, which function as key regulators of mitosis and programmed cell death, and is overexpressed in many tumor types. The mechanism of cytotoxic effect is partially due to the inhibition of IAP gene expression.
  
  
  
  These findings indicated that GW843682X exhibited remarkable cytotoxic effects on nasopharyngeal carcinoma 5-8F cells by down-regulating IAP gene expression, suggesting that GW843682X may become a novel therapeutic agent for nasopharyngeal carcinoma.
authors.forename: Qinyong
authors.initials: Q
authors.lastname: Hu
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Chu
authors.forename: Weiguo
authors.initials: W
authors.lastname: Hu
authors.affiliation: Wuhan University Renmin hospital, Cancer center, Jiefang Road NO.238, Wuhan, China. mpeng320@whu.edu.cn.
authors.forename: Min
authors.initials: M
authors.lastname: Peng
authors.affiliation: . qibinsong@163.com.
authors.forename: Qibin
authors.initials: Q
authors.lastname: Song
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002277:Carcinoma / Q000188:drug therapy* / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: C524135:5-(5,6-dimethoxy-1H-benzimidazol-1-yl)-3-((2-(trifluoromethyl)benzyl)oxy)thiophene-2-carboxamide; D000970:Antineoplastic Agents; D001562:Benzimidazoles; D013876:Thiophenes