Overexpression of cyclin B1 antagonizes chemotherapeutic-induced apoptosis through PTEN/Akt pathway in human esophageal squamous cell carcinoma cells

Cancer Biol Ther. 2013 Jan;14(1):45-55. doi: 10.4161/cbt.22627. Epub 2012 Oct 31.

Abstract

The role of cyclin B1 in the clinical therapeutic sensitivity of human esophageal squamous cell carcinoma (ESCC) remains to be defined. In this study, we found that elevated cyclin B1 expression attenuated the apoptosis induced by cisplatin or paclitaxel, while knockdown of cyclin B1 enhanced cisplatin or paclitaxel sensitivity in ESCC cells. Cyclin B1-mediated apoptosis may rely on the Bcl-2-dependent mitochondria-regulated intrinsic death pathway, and the antagonizing effect of cyclin B1 on chemotherapeutic agent-induced apoptosis was through PTEN/Akt pathway. Therefore, cyclin B1 might be a therapeutic target for the development of specific and efficient approaches in the treatment of ESCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects*
  • Carcinoma, Squamous Cell / drug therapy*
  • Caspases / metabolism
  • Cell Line, Tumor / drug effects
  • Cell Survival / drug effects
  • Chromones / pharmacology
  • Cisplatin / pharmacology
  • Cyclin B1 / genetics
  • Cyclin B1 / metabolism*
  • Drug Resistance, Neoplasm
  • Esophageal Neoplasms / drug therapy*
  • Gene Knockdown Techniques
  • Humans
  • Morpholines / pharmacology
  • PTEN Phosphohydrolase / metabolism*
  • Paclitaxel / pharmacology
  • Phosphoinositide-3 Kinase Inhibitors
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • RNA, Small Interfering / genetics
  • Signal Transduction

Substances

  • Antineoplastic Agents
  • CCNB1 protein, human
  • Chromones
  • Cyclin B1
  • Morpholines
  • Phosphoinositide-3 Kinase Inhibitors
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Small Interfering
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • Proto-Oncogene Proteins c-akt
  • PTEN Phosphohydrolase
  • PTEN protein, human
  • Caspases
  • Paclitaxel
  • Cisplatin