title: The combination effect of amrubicin with cisplatin or irinotecan for small-cell lung cancer cells.
abstract: The single agent of amrubicin is active in untreated small-cell lung cancer (SCLC). Cytotoxicity of amrubicinol, the active form of amrubicin, was evaluated in a parent SCLC cell line (SBC-3); an active metabolite of irinotecan, 7-ethyl-10-hydroxy-camptothecin (SN-38)-resistant subline (SBC-3/SN-38); and cisplatin-resistant subline (SBC-3/CDDP) using AlamarBlue assay. Interaction of the combined drugs was evaluated by median-effect plot analysis, and the fraction of apoptotic cells was determined using flow cytometry. SBC-3/SN-38 was 34-fold more resistant to SN-38 and SBC-3/CDDP was 7.2-fold more resistant to cisplatin than parental SBC-3. However, these resistant sublines retained sensitivity to amrubicinol (1.8- and 1.7-fold, respectively). Simultaneous exposure of SBC-3/SN-38 cells to amrubicinol and cisplatin showed a synergistic effect. Simultaneous exposure of SBC-3/CDDP cells to amrubicinol and SN-38 displayed synergistic or additive effects. The two-drug combination produced an increase of apoptotic cells compared to each single agent alone in both resistant cells. These findings suggest that amrubicin alone and in combination with cisplatin or irinotecan is effective against SCLC refractory to irinotecan and/or cisplatin.
authors.affiliation: Department of Respiratory Medicine, Okayama University Hospital, Okayama 700-8558, Japan. ntakigaw@md.okayama-u.ac.jp
authors.forename: Nagio
authors.initials: N
authors.lastname: Takigawa
authors.forename: Masako
authors.initials: M
authors.lastname: Takeyama
authors.forename: Takuo
authors.initials: T
authors.lastname: Shibayama
authors.forename: Atsuhiko
authors.initials: A
authors.lastname: Tada
authors.forename: Noriko
authors.initials: N
authors.lastname: Kawata
authors.forename: Chiharu
authors.initials: C
authors.lastname: Okada
authors.forename: Keisuke
authors.initials: K
authors.lastname: Aoe
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Kozuki
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Hotta
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tabata
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Kiura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ueoka
authors.forename: Mitsune
authors.initials: M
authors.lastname: Tanimoto
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Takahashi
mesh_terms: D018943:Anthracyclines / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology; D018288:Carcinoma, Small Cell / Q000473:pathology / Q000503:physiopathology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D006801:Humans; D020128:Inhibitory Concentration 50; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000473:pathology / Q000503:physiopathology
chemical_list: D018943:Anthracyclines; D000970:Antineoplastic Agents; D000077146:Irinotecan; C055866:amrubicin; D002945:Cisplatin; D002166:Camptothecin