[Targeted degradation of epidermal growth factor receptor in nasopharyngeal carcinoma by chimeric molecule]

Lin Chuang Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2017 Feb 20;31(4):297-300. doi: 10.13201/j.issn.1001-1781.2017.04.012.
[Article in Chinese]

Abstract

Objective:The aim of this study was to investigate targeted degradation of the epidermal growth factor receptor (EGFR) by chimeric molecules (EGF-PROTAC) via the ubiquitin-proteasome pathway on human nasopharyngeal carcinoma CNE-2 cells and demonstrate the regulative effect on the proliferation and apoptosis of the CNE-2 cells.Method:After the EGF-PROTAC treating CNE-2 cells in vitro, the biological effects of the EGF-PROTAC was detected by western blot, CKK-8 assay, flow cytometry and Transwell migration assay in CNE-2 cells.Result:The expression level of EGFR proteins in the EGF-PROTAC treated group was lower than the control group (P< 0.05); CKK-8 assay results showed that CNE-2 cells survival rate at 3, 6, 9 and 12h decreased greatly than the control group (P< 0.05); Flow cytometry indicated that the apoptosis index of the CNE-2 cells in EGF-PROTAC treated group was significantly higher than the control group (P< 0.05); The invasion ability detected that the number of CNE-2 cells in the EGF-PROTAC treated group was significantly lower than the control group (P< 0.05).Conclusion:The chimeric molecule (EGF-PROTAC) can target the degradation of epidermal growth factor receptors (EGFR) and effectively inhibit the growth of the CNE-2 cells and promote apoptosis in vitro.

Keywords: chimeric molecule; epidermal growth factor receptor; nasopharyngeal neoplasms; ubiquitination.

MeSH terms

  • Apoptosis
  • Carcinoma / drug therapy
  • Carcinoma / metabolism*
  • Carcinoma / pathology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • ErbB Receptors
  • Humans
  • Nasopharyngeal Carcinoma
  • Nasopharyngeal Neoplasms / drug therapy
  • Nasopharyngeal Neoplasms / metabolism*
  • Nasopharyngeal Neoplasms / pathology*
  • Proteasome Endopeptidase Complex / metabolism
  • Recombinant Fusion Proteins / metabolism*
  • Ubiquitin / metabolism*

Substances

  • Recombinant Fusion Proteins
  • Ubiquitin
  • chimeric p53 protein
  • ErbB Receptors
  • Proteasome Endopeptidase Complex