Determinants of cisplatin and irinotecan activities in human lung adenocarcinoma cells: Evidence of cisplatin accumulation and topoisomerase I activity

Tadashi Matsumura, Nagio Takigawa, Katsuyuki Kiura, Takuo Shibayama, Masakazu Chikamori, Masahiro Tabata, Hiroshi Ueoka, Mitsune Tanimoto

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

To elucidate the sensitivity of adenocarcinoma of the lung to cisplatin and irinotecan, intracellular glutathione (GSH) and glutathione S-transferase (GST)-π concentrations and topoisomerase (topo) I activity were investigated using six adenocarcinoma cell lines. The antiproliferative activity was determined by MTT assay in terms of inhibition concentration (IC50) values. The IC50 values to cisplatin were not correlated with the amounts of intracellular GSH or GST-π, but with intracellular accumulation of platinum (r=-0.91, p=0.013). IC50 values to SN-38 were correlated with topo I activity determined by relaxation assay of pBR322 (r=-0.83, p=0.040). These results suggest that platinum accumulation and topo I activity have definite impacts on the sensitivity of lung adenocarcinoma to cisplatin and irinotecan, respectively.

Original languageEnglish
Pages (from-to)717-722
Number of pages6
JournalIn Vivo
Volume19
Issue number4
Publication statusPublished - Jul 2005

Keywords

  • Adenocarcinoma
  • Cisplatin
  • Drug sensitivity
  • Irinotecan
  • Lung neoplasms
  • Topoisomerase I

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology

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