Determinants of cisplatin and irinotecan activities in human lung adenocarcinoma cells: evidence of cisplatin accumulation and topoisomerase I activity.
To elucidate the sensitivity of adenocarcinoma of the lung to cisplatin and irinotecan, intracellular glutathione (GSH) and glutathione S-transferase (GST)-pi 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-pi, 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.
Department of Respiratory Medicine (Thoracic Oncology), Okayama University Hospital, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
Tadashi
T
Matsumura
Nagio
N
Takigawa
Katsuyuki
K
Kiura
Takuo
T
Shibayama
Masakazu
M
Chikamori
Masahiro
M
Tabata
Hiroshi
H
Ueoka
Mitsune
M
Tanimoto
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor / Q000187:drug effects / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D004264:DNA Topoisomerases, Type I / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005562:Formazans / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D010984:Platinum / Q000378:metabolism; D013778:Tetrazolium Salts / Q000378:metabolism
D000970:Antineoplastic Agents; D005562:Formazans; D013778:Tetrazolium Salts; C079782:MTT formazan; D010984:Platinum; D000077146:Irinotecan; D005982:Glutathione Transferase; D004264:DNA Topoisomerases, Type I; D005978:Glutathione; D002945:Cisplatin; D002166:Camptothecin