Determinants of Cisplatin and Irinotecan Activities in Human Lung Adenocarcinoma Cells: Evidence of Cisplatin Accumulation and Topoisomerase I Activity

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.