Chk1 inhibitor Gö6976 enhances the sensitivity of nasopharyngeal carcinoma cells to radiotherapy and chemotherapy in vitro and in vivo

Cancer Lett. 2010 Nov 28;297(2):190-7. doi: 10.1016/j.canlet.2010.05.011. Epub 2010 Jul 8.

Abstract

Nasopharyngeal carcinoma (NPC) is a malignant tumor. This type of carcinoma has a low 5-year patient survival rate. Thus, there is a need for improved therapeutics. We determined that the Chk1 inhibitor Gö6976 enhanced the sensitivity of CNE1 and CNE2 cells to ionizing radiation (IR) or cisplatin by abrogating S and G(2)/M arrest and subsequently promoting apoptosis. Furthermore, Gö6976 appeared to sensitize NPC xenografts in nude mice to IR or cisplatin treatment. This is the first report to show that the Chk1 inhibitor Gö6976 sensitizes NPC cells to treatment using in vitro and in vivo models.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carbazoles / pharmacology*
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Checkpoint Kinase 1
  • Cisplatin / pharmacology*
  • Drug Synergism
  • Humans
  • Infrared Rays
  • Mice
  • Mice, Nude
  • Nasopharyngeal Neoplasms / drug therapy*
  • Nasopharyngeal Neoplasms / enzymology
  • Nasopharyngeal Neoplasms / pathology
  • Nasopharyngeal Neoplasms / radiotherapy*
  • Protein Kinase Inhibitors / pharmacology*
  • Protein Kinases / metabolism*
  • Xenograft Model Antitumor Assays

Substances

  • Carbazoles
  • Protein Kinase Inhibitors
  • Go 6976
  • Protein Kinases
  • CHEK1 protein, human
  • Checkpoint Kinase 1
  • Chek1 protein, mouse
  • Cisplatin