Efficacy of combination treatment and influence of schedule with irinotecan and amrubicin in human lung carcinoma cells in vivo and in vitro.
The aim of this study was to elucidate the efficacy of combination therapy with irinotecan and amrubicin for lung cancer and the influence of administration schedule in a xenograft mouse model and human cancer cell culture. We investigated the antitumor activity of irinotecan and amrubicin on human small cell lung cancer cell line LX-1 inoculated in mice in vivo and the cytotoxic effect of SN-38 and amrubicinol on human lung cancer cell lines A549 and PC-6 in vitro. Combined administration of irinotecan and amrubicin in divided doses inhibited tumor growth by approximately 90%, with complete recovery observed in one case. Furthermore, combined administration in divided doses induced little loss of body weight. Combination index analysis revealed that the cell growth inhibitory effect of SN-38 combined with amrubicinol was additive, regardless of schedule or cell line. The effect of combination treatment with SN-38 and amrubicinol on cell cycle was investigated. Cell cycle showed arrest at both the S and G2/M phases. The results indicate that combination therapy with irinotecan and amrubicin can be expected to yield improved outcomes, including less toxicity, especially with divided administration.
Shishido
Yoshiyuki
Y
Yakult Central Institute for Microbiological Research, Kunitachi, Tokyo 186-8650, Japan. yoshiyuki-shishido@yakult.co.jp
Furuta
Tomio
T
Matsuzaki
Takeshi
T
Nagata
Hiroshi
H
Hashimoto
Shusuke
S
D000818:Animals; D018943:Anthracyclines / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000494:pharmacology*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D006801:Humans; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D014183:Transplantation, Heterologous
D018943:Anthracyclines; D000077146:Irinotecan; C055866:amrubicin; D002166:Camptothecin