title: [Correlation between ras gene and the resistance of nasopharyngeal carcinoma to cetuximab].
abstract: OBJECTIVE
  To explore the correlation of ras gene to the drug resistance of nasopharyngeal carcinoma to cetuximab.
  
  
  METHODS
  Cultured 5-8F/Erbitux cells were induced by stepwise exposure to increasing doses of cetuximab. MTT assay was used to determine the IC50 (half inhibitory concentration) of cetuximab and the drug resistance index (RI). Western blotting was employed to detect the protein levels of H-ras and K-ras. Real-time PCR was used to detect the expression of H-ras and K-ras. Gene sequencing was performed to identify potential mutations in H-ras and K-ras genes.
  
  
  RESULTS
  We successfully induced cetuximab-resistant 5-8F/Erbitux hNPC cells by stepwise exposure to increasing doses of cetuximab. After treatment with cetuximab for 3 and 5 days, the RI of 5-8F/Erbitux cells was 1.2 and 1.1, respectively. The 5-8F/Erbitux cells had increased levels of H-ras and K-ras protein expressions (P<0.001) and enhanced gene expressions of H-ras (P=0.016) and ras-p21 (P=0.113) with decreased K-ras gene expression (P=0.000). Sequence analysis identified no mutations in the H-ras and K-ras genes in codons 12, 13, 59, and 61.
  
  
  CONCLUSIONS
  Gene amplification and overexpression of H-ras is the major mechanism that causes the drug resistance of 5-8F/Erbitux cells to cetuximab.
authors.affiliation: Cancer Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. nfyyzq@126.com
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zuo
authors.forename: Rong-cheng
authors.initials: RC
authors.lastname: Luo
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D045744:Cell Line, Tumor; D000068818:Cetuximab; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000473:pathology*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068818:Cetuximab