Effect of combined treatment with micelle-incorporated cisplatin (NC-6004) and S-1 on human gastric cancer xenografts

Kudo,Masahisa; Yamamoto,Yoshiyuki; Koga,Yoshikatsu; Hamaguchi,Tetsuya; Akimoto,Tetsuo; Yasunaga,Masahiro; Matsumura,Yasuhiro

doi:10.3892/mco.2016.1070

December-2016 Volume 5 Issue 6

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December-2016 Volume 5 Issue 6

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Article

Effect of combined treatment with micelle-incorporated cisplatin (NC-6004) and S-1 on human gastric cancer xenografts

Authors:
- Masahisa Kudo
- Yoshiyuki Yamamoto
- Yoshikatsu Koga
- Tetsuya Hamaguchi
- Tetsuo Akimoto
- Masahiro Yasunaga
- Yasuhiro Matsumura
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Affiliations: Division of Developmental Therapeutics, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Chiba 277‑8577, Japan, Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo 104‑0045, Japan, Course of Advanced Clinical Research of Cancer, Juntendo University Graduate School of Medicine, Tokyo 113‑8421, Japan
Pages: 817-822
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Published online on: November 1, 2016

https://doi.org/10.3892/mco.2016.1070
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Abstract

Combination therapy with S-1 and cisplatin (CDDP) is the standard chemotherapy for advanced gastric cancer in Japan; however, its administration requires hospitalization for hydration to prevent nephrotoxicity from CDDP. By contrast, NC‑6004 appears to reduce the renal toxicity of CDDP and may be used on an outpatient basis. Thus, the effects of combined treatment with S‑1 and NC‑6004 were compared with those of S‑1 and CDDP in a human gastric cancer model. In vitro cytotoxic effects were investigated in 44As3Luc, MKN45 and MKN74 human gastric cancer cell lines. The effects of NC‑6004 and 5-fluorouracil (5‑FU) were compared with the effects of CDDP and 5‑FU using the combination index method. The in vivo antitumor effects of S‑1/NC‑6004 and S‑1/CDDP were evaluated in mice bearing 44As3Luc xenografts. Both combinations exhibited synergistic activity in MKN45 and MKN74 cells and additive effects in 44As3Luc cells. Moreover, the in vivo antitumor effects did not differ between the S‑1/NC‑6004 and S‑1/CDDP treatment groups. However, a significantly lower body weight loss was observed in S-1/NC-6004-treated mice compared with the S‑1/CDDP‑treated mice. Our data warrant a clinical evaluation of S‑1/NC‑6004 combination therapy.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Effect of combined treatment with micelle-incorporated cisplatin (NC-6004) and S-1 on human gastric cancer xenografts

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