Cellular sensitivity determinants to docetaxel in human gastrointestinal cancers

Int J Oncol. 2002 Feb;20(2):333-8.

Abstract

beta-tubulin (beta-TUB), Bcl-XL, and additionally glutathione S-transferase pi (GSTpi) were found to participate in sensitivity to docetaxel (TXT) in 7 human gastrointestinal cancer cell lines. The gene expression level of beta-TUB, Bcl-XL, and GSTpi was closely correlated with the IC50 for TXT. beta-TUB amount related to TXT resistance, and GST activity was correlated with IC50 for TXT in the 30-min treatment setting. Bcl-XL transfection increased TXT resistance of COLO201 cells, whereas GST inhibition by ethacrynic acid enhanced TXT cytotoxicity. Continuous TXT treatment increased beta-TUB and GSTpi expression, but the increased GSTpi mRNA was observed in TXT-resistant HCC-48 cells alone.

MeSH terms

  • Cell Division / drug effects
  • Docetaxel
  • Ethacrynic Acid / pharmacology
  • Flow Cytometry
  • Gastrointestinal Neoplasms / drug therapy
  • Gastrointestinal Neoplasms / enzymology
  • Gastrointestinal Neoplasms / genetics*
  • Gastrointestinal Neoplasms / pathology*
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Genes, p53 / genetics
  • Glutathione S-Transferase pi
  • Glutathione Transferase / genetics
  • Humans
  • Inhibitory Concentration 50
  • Isoenzymes / genetics
  • Paclitaxel / administration & dosage
  • Paclitaxel / analogs & derivatives*
  • Paclitaxel / pharmacology*
  • Paclitaxel / therapeutic use
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Taxoids*
  • Time Factors
  • Transfection
  • Tubulin / genetics
  • Tumor Cells, Cultured
  • bcl-X Protein

Substances

  • BCL2L1 protein, human
  • Isoenzymes
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • Taxoids
  • Tubulin
  • bcl-X Protein
  • Docetaxel
  • GSTP1 protein, human
  • Glutathione S-Transferase pi
  • Glutathione Transferase
  • Ethacrynic Acid
  • Paclitaxel