The combination effect of amrubicin with cisplatin or irinotecan for small-cell lung cancer cells.
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.
Takigawa
Nagio
N
Department of Respiratory Medicine, Okayama University Hospital, Okayama 700-8558, Japan. ntakigaw@md.okayama-u.ac.jp
Takeyama
Masako
M
Shibayama
Takuo
T
Tada
Atsuhiko
A
Kawata
Noriko
N
Okada
Chiharu
C
Aoe
Keisuke
K
Kozuki
Toshiyuki
T
Hotta
Katsuyuki
K
Tabata
Masahiro
M
Kiura
Katsuyuki
K
Ueoka
Hiroshi
H
Tanimoto
Mitsune
M
Takahashi
Kiyoshi
K
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
D018943:Anthracyclines; D000970:Antineoplastic Agents; D000077146:Irinotecan; C055866:amrubicin; D002945:Cisplatin; D002166:Camptothecin