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.
Matsumura
Tadashi
T
Department of Respiratory Medicine (Thoracic Oncology), Okayama University Hospital, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
Takigawa
Nagio
N
Kiura
Katsuyuki
K
Shibayama
Takuo
T
Chikamori
Masakazu
M
Tabata
Masahiro
M
Ueoka
Hiroshi
H
Tanimoto
Mitsune
M
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