論文 - 詳細
RRC ID | 38595 |
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著者 | Morisaki T, Onishi H, Koya N, Kiyota A, Tanaka H, Umebayashi M, Ogino T, Nagamatsu I, Katano M. |
タイトル | Combinatorial cytotoxicity of gemcitabine and cytokine-activated killer cells in hepatocellular carcinoma via the NKG2D-MICA/B system. |
ジャーナル | Anticancer Res |
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. |
巻・号 | 31(7) |
ページ | 2505-10 |
公開日 | 2011-7-1 |
PII | 31/7/2505 |
PMID | 21873167 |
MeSH | Antimetabolites, Antineoplastic / pharmacology* Carcinoma, Hepatocellular / blood Carcinoma, Hepatocellular / pathology* Carcinoma, Hepatocellular / therapy Cell Line, Tumor / drug effects Cell Line, Tumor / immunology Cells, Cultured / drug effects Combined Modality Therapy Cytotoxicity, Immunologic Deoxycytidine / analogs & derivatives* Deoxycytidine / pharmacology Flow Cytometry Gemcitabine Gene Expression Regulation, Neoplastic / drug effects Histocompatibility Antigens Class I / biosynthesis* Histocompatibility Antigens Class I / genetics Humans In Vitro Techniques Interleukin-2 / pharmacology Liver Neoplasms / blood Liver Neoplasms / pathology* Liver Neoplasms / therapy Monocytes, Activated Killer / immunology* Muromonab-CD3 / pharmacology NK Cell Lectin-Like Receptor Subfamily K / immunology* Recombinant Proteins / pharmacology |
IF | 1.994 |
引用数 | 31 |
WOS 分野 | ONCOLOGY |
リソース情報 | |
ヒト・動物細胞 |