Combinatorial cytotoxicity of gemcitabine and cytokine-activated killer cells in hepatocellular carcinoma via the NKG2D-MICA/B system

Takashi Morisaki, Hideya Ohnishi, Norihiro Koya, Akifumi Kiyota, Hiroto Tanaka, Masayo Umebayashi, Toshitatsu Ogino, Iori Nagamatsu, Mitsuo Katano

研究成果: ジャーナルへの寄稿記事

32 引用 (Scopus)

抄録

Aim: Natural-killer group 2, member D (NKG2D) is an activating receptor on natural killer cells and activated T-cells, designated cytokine-activated killer (CAK) cells here. The MHC class I chain-related A and B (MICA and MICB, respectively) are ligands of NKG2D and are expressed on various human tumor cells, including hepatocellular carcinoma (HCC) cells. Here, we investigate whether gemcitabine, a chemotherapeutic agent, affects MICA/B expression in HCC. Materials and Methods: We used ELISA, RT-PCR and adherent target detachment assays to determine expression of MICA/B in HepG2 HCC cells and the level of cellular cytotoxicity generated by treatment with gemcitabine and/or CAK cells. Results: Surface expression of MICA/B was evident after gemcitabine treatment, and MICB-specific mRNA was up-regulated. Pre-treatment with gemcitabine and subsequent exposure to CAK cells induced greater cytotoxicity than either treatment alone. Inclusion of soluble MICB significantly reduced cytotoxicity. Conclusion: Gemcitabine induced MICA/B expression in HepG2 cells, resulting in synergistic enhancement of the cytotoxic effects of NKG2D-high CAK cells. The combination of gemcitabine and CAK cells may have clinical therapeutic significance for HCC.

元の言語英語
ページ(範囲)2505-2510
ページ数6
ジャーナルAnticancer Research
31
発行部数7
出版物ステータス出版済み - 7 2011

Fingerprint

gemcitabine
Hepatocellular Carcinoma
Cytokines
Cytokine-Induced Killer Cells
Natural Killer Cell Receptors
Therapeutics
Hep G2 Cells
Enzyme-Linked Immunosorbent Assay

All Science Journal Classification (ASJC) codes

  • Cancer Research
  • Oncology

これを引用

Combinatorial cytotoxicity of gemcitabine and cytokine-activated killer cells in hepatocellular carcinoma via the NKG2D-MICA/B system. / Morisaki, Takashi; Ohnishi, Hideya; Koya, Norihiro; Kiyota, Akifumi; Tanaka, Hiroto; Umebayashi, Masayo; Ogino, Toshitatsu; Nagamatsu, Iori; Katano, Mitsuo.

:: Anticancer Research, 巻 31, 番号 7, 07.2011, p. 2505-2510.

研究成果: ジャーナルへの寄稿記事

Morisaki, T, Ohnishi, H, Koya, N, Kiyota, A, Tanaka, H, Umebayashi, M, Ogino, T, Nagamatsu, I & Katano, M 2011, 'Combinatorial cytotoxicity of gemcitabine and cytokine-activated killer cells in hepatocellular carcinoma via the NKG2D-MICA/B system', Anticancer Research, 巻. 31, 番号 7, pp. 2505-2510.
Morisaki, Takashi ; Ohnishi, Hideya ; Koya, Norihiro ; Kiyota, Akifumi ; Tanaka, Hiroto ; Umebayashi, Masayo ; Ogino, Toshitatsu ; Nagamatsu, Iori ; Katano, Mitsuo. / Combinatorial cytotoxicity of gemcitabine and cytokine-activated killer cells in hepatocellular carcinoma via the NKG2D-MICA/B system. :: Anticancer Research. 2011 ; 巻 31, 番号 7. pp. 2505-2510.
@article{2e35f81e47a24e78bcee2fdc98b0d9e7,
title = "Combinatorial cytotoxicity of gemcitabine and cytokine-activated killer cells in hepatocellular carcinoma via the NKG2D-MICA/B system",
abstract = "Aim: Natural-killer group 2, member D (NKG2D) is an activating receptor on natural killer cells and activated T-cells, designated cytokine-activated killer (CAK) cells here. The MHC class I chain-related A and B (MICA and MICB, respectively) are ligands of NKG2D and are expressed on various human tumor cells, including hepatocellular carcinoma (HCC) cells. Here, we investigate whether gemcitabine, a chemotherapeutic agent, affects MICA/B expression in HCC. Materials and Methods: We used ELISA, RT-PCR and adherent target detachment assays to determine expression of MICA/B in HepG2 HCC cells and the level of cellular cytotoxicity generated by treatment with gemcitabine and/or CAK cells. Results: Surface expression of MICA/B was evident after gemcitabine treatment, and MICB-specific mRNA was up-regulated. Pre-treatment with gemcitabine and subsequent exposure to CAK cells induced greater cytotoxicity than either treatment alone. Inclusion of soluble MICB significantly reduced cytotoxicity. Conclusion: Gemcitabine induced MICA/B expression in HepG2 cells, resulting in synergistic enhancement of the cytotoxic effects of NKG2D-high CAK cells. The combination of gemcitabine and CAK cells may have clinical therapeutic significance for HCC.",
author = "Takashi Morisaki and Hideya Ohnishi and Norihiro Koya and Akifumi Kiyota and Hiroto Tanaka and Masayo Umebayashi and Toshitatsu Ogino and Iori Nagamatsu and Mitsuo Katano",
year = "2011",
month = "7",
language = "English",
volume = "31",
pages = "2505--2510",
journal = "Anticancer Research",
issn = "0250-7005",
publisher = "International Institute of Anticancer Research",
number = "7",

}

TY - JOUR

T1 - Combinatorial cytotoxicity of gemcitabine and cytokine-activated killer cells in hepatocellular carcinoma via the NKG2D-MICA/B system

AU - Morisaki, Takashi

AU - Ohnishi, Hideya

AU - Koya, Norihiro

AU - Kiyota, Akifumi

AU - Tanaka, Hiroto

AU - Umebayashi, Masayo

AU - Ogino, Toshitatsu

AU - Nagamatsu, Iori

AU - Katano, Mitsuo

PY - 2011/7

Y1 - 2011/7

N2 - Aim: Natural-killer group 2, member D (NKG2D) is an activating receptor on natural killer cells and activated T-cells, designated cytokine-activated killer (CAK) cells here. The MHC class I chain-related A and B (MICA and MICB, respectively) are ligands of NKG2D and are expressed on various human tumor cells, including hepatocellular carcinoma (HCC) cells. Here, we investigate whether gemcitabine, a chemotherapeutic agent, affects MICA/B expression in HCC. Materials and Methods: We used ELISA, RT-PCR and adherent target detachment assays to determine expression of MICA/B in HepG2 HCC cells and the level of cellular cytotoxicity generated by treatment with gemcitabine and/or CAK cells. Results: Surface expression of MICA/B was evident after gemcitabine treatment, and MICB-specific mRNA was up-regulated. Pre-treatment with gemcitabine and subsequent exposure to CAK cells induced greater cytotoxicity than either treatment alone. Inclusion of soluble MICB significantly reduced cytotoxicity. Conclusion: Gemcitabine induced MICA/B expression in HepG2 cells, resulting in synergistic enhancement of the cytotoxic effects of NKG2D-high CAK cells. The combination of gemcitabine and CAK cells may have clinical therapeutic significance for HCC.

AB - Aim: Natural-killer group 2, member D (NKG2D) is an activating receptor on natural killer cells and activated T-cells, designated cytokine-activated killer (CAK) cells here. The MHC class I chain-related A and B (MICA and MICB, respectively) are ligands of NKG2D and are expressed on various human tumor cells, including hepatocellular carcinoma (HCC) cells. Here, we investigate whether gemcitabine, a chemotherapeutic agent, affects MICA/B expression in HCC. Materials and Methods: We used ELISA, RT-PCR and adherent target detachment assays to determine expression of MICA/B in HepG2 HCC cells and the level of cellular cytotoxicity generated by treatment with gemcitabine and/or CAK cells. Results: Surface expression of MICA/B was evident after gemcitabine treatment, and MICB-specific mRNA was up-regulated. Pre-treatment with gemcitabine and subsequent exposure to CAK cells induced greater cytotoxicity than either treatment alone. Inclusion of soluble MICB significantly reduced cytotoxicity. Conclusion: Gemcitabine induced MICA/B expression in HepG2 cells, resulting in synergistic enhancement of the cytotoxic effects of NKG2D-high CAK cells. The combination of gemcitabine and CAK cells may have clinical therapeutic significance for HCC.

UR - http://www.scopus.com/inward/record.url?scp=79961185621&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79961185621&partnerID=8YFLogxK

M3 - Article

VL - 31

SP - 2505

EP - 2510

JO - Anticancer Research

JF - Anticancer Research

SN - 0250-7005

IS - 7

ER -