Establishment and characterization of multidrug-resistant gastric cancer cell lines

Anticancer Res. 2010 Mar;30(3):915-21.

Abstract

Aim: The aim of this study was to establish drug-resistant cell lines and to elucidate mechanisms leading to multi-drug resistance in gastric cancer.

Materials and methods: Five cancer cell lines resistant to 5-fluorouracil, paclitaxel, oxaliplatin, irinotecan, or gemcitabine, were respectively established from a parent gastric cancer cell line, OCUM-2M, by stepwise exposure to each chemotherapeutical agent.

Results: Cell death by apoptosis induced by anti-cancer drugs was low in 5 chemo-resistant cell lines. Percentage of cells in S and G(0)/G(1) phase was low in cell lines resistant to oxaliplatin or irinotecan. Cell lines resistant to paclitaxel, oxaliplatin, and gemcitabine showed multi-drug resistance. Alterations in MRP, DAPK1, or DAPK2 expression were found in multi-drug resistant cell lines.

Conclusion: The cell-cycle distribution and alterations of MRP, DAPK1, and DAPK2 genes may be integral part of mechanisms responsible for chemo-resistance. These cell lines might be useful to study molecular mechanisms leading to multi-drug resistance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / biosynthesis
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Apoptosis / drug effects
  • Apoptosis / physiology
  • Apoptosis Regulatory Proteins / biosynthesis
  • Calcium-Calmodulin-Dependent Protein Kinases / biosynthesis
  • Camptothecin / analogs & derivatives
  • Camptothecin / pharmacology
  • Cell Cycle / drug effects
  • Cell Cycle / physiology
  • Cell Line, Tumor*
  • Death-Associated Protein Kinases
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / pharmacology
  • Drug Resistance, Multiple
  • Drug Resistance, Neoplasm
  • Gemcitabine
  • Humans
  • Irinotecan
  • Organoplatinum Compounds / pharmacology
  • Oxaliplatin
  • Paclitaxel / pharmacology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology*

Substances

  • ATP Binding Cassette Transporter, Subfamily B
  • Antineoplastic Agents, Phytogenic
  • Apoptosis Regulatory Proteins
  • Organoplatinum Compounds
  • Oxaliplatin
  • Deoxycytidine
  • Irinotecan
  • DAPK1 protein, human
  • DAPK2 protein, human
  • Death-Associated Protein Kinases
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Paclitaxel
  • Camptothecin
  • Gemcitabine