RRC ID 38595
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