CDK4 down-regulation induced by paclitaxel is associated with G1 arrest in gastric cancer cells

Clin Cancer Res. 1998 Dec;4(12):3063-8.

Abstract

Paclitaxel induces a cell cycle block at G2-M phase by preventing the depolymerization of microtubules and induces p53-independent apoptosis in many cancer cells. We observed that gastric cancer cells treated with paclitaxel have shown a cyclin-dependent kinase (CDK)4 down-regulation. This paclitaxel-induced CDK4 down-regulation resulted in a cell cycle arrest at G1-S phase. To confirm this observation, we prepared stable transfectants that overexpressed CDK4 and analyzed the cell cycle progression. Ectopic expression of CDK4 in SNU cells resulted in a release of paclitaxel-induced G1 arrest. The release of G1 arrest by enforced expression of CDK4 seems to make the cells more sensitive to paclitaxel-induced apoptosis. From this finding, we could then suggest that paclitaxel treatment induces both G1-S and G2-M blocks in the cell cycle progression of gastric cancer cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinases / metabolism*
  • Down-Regulation / drug effects*
  • G1 Phase / drug effects*
  • G2 Phase / drug effects
  • Humans
  • Paclitaxel / pharmacology*
  • Proto-Oncogene Proteins*
  • S Phase / drug effects
  • Stomach Neoplasms / drug therapy
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology*
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents, Phytogenic
  • Proto-Oncogene Proteins
  • CDK4 protein, human
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinases
  • Paclitaxel