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

doi:10.3892/or.15.4.837

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

University Hospital

Research output: Contribution to journal › Article › peer-review

7 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 language	English
Pages (from-to)	837-842
Number of pages	6
Journal	Oncology reports
Volume	15
Issue number	4
DOIs	https://doi.org/10.3892/or.15.4.837
Publication status	Published - Apr 2006

Keywords

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

ASJC Scopus subject areas

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3892/or.15.4.837

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@article{df31f240abf9424198b496c35e95a518,

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.",

keywords = "Amrubicin, Cisplatin, Irinotecan, Median-effect plot analysis, Small-cell lung cancer",

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

year = "2006",

month = apr,

doi = "10.3892/or.15.4.837",

language = "English",

volume = "15",

pages = "837--842",

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T1 - The combination effect of amrubicin with cisplatin or irinotecan for small-cell lung cancer cells

AU - Takigawa, Nagio

AU - Takeyama, Masako

AU - Shibayama, Takuo

AU - Tada, Atsuhiko

AU - Kawata, Noriko

AU - Okada, Chiharu

AU - Aoe, Keisuke

AU - Kozuki, Toshiyuki

AU - Hotta, Katsuyuki

AU - Tabata, Masahiro

AU - Kiura, Katsuyuki

AU - Ueoka, Hiroshi

AU - Tanimoto, Mitsune

AU - Takahashi, Kiyoshi

PY - 2006/4

Y1 - 2006/4

N2 - 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.

AB - 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.

KW - Amrubicin

KW - Cisplatin

KW - Irinotecan

KW - Median-effect plot analysis

KW - Small-cell lung cancer

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C2 - 16525668

AN - SCOPUS:33746390166

SN - 1021-335X

VL - 15

SP - 837

EP - 842

JO - Oncology Reports

JF - Oncology Reports

IS - 4

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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