The combination effect of amrubicin with cisplatin or irinotecan for small-cell lung cancer cells

Nagio Takigawa, Masako Takeyama, Takuo Shibayama, Atsuhiko Tada, Noriko Kawata, Chiharu Okada, Keisuke Aoe, Toshiyuki Kozuki, Katsuyuki Hotta, Masahiro Tabata, Katsuyuki Kiura, Hiroshi Ueoka, Mitsune Tanimoto, Kiyoshi Takahashi

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)837-842
Number of pages6
JournalOncology reports
Volume15
Issue number4
DOIs
Publication statusPublished - Apr 2006

Keywords

  • Amrubicin
  • Cisplatin
  • Irinotecan
  • Median-effect plot analysis
  • Small-cell lung cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Takigawa, N., Takeyama, M., Shibayama, T., Tada, A., Kawata, N., Okada, C., Aoe, K., Kozuki, T., Hotta, K., Tabata, M., Kiura, K., Ueoka, H., Tanimoto, M., & Takahashi, K. (2006). The combination effect of amrubicin with cisplatin or irinotecan for small-cell lung cancer cells. Oncology reports, 15(4), 837-842. https://doi.org/10.3892/or.15.4.837