Fukuoka General Cancer Clinic, 3-1-1 Sumiyoshi, Hakata-ku, Fukuoka 812-0018, Japan.
Anticancer Res. 2011 Jul;31(7):2505-10.
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.
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.
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.
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.
自然杀伤细胞 2 组，成员 D（NKG2D）是自然杀伤细胞和活化 T 细胞上的一种激活受体，这里将其指定为细胞因子激活的杀伤（CAK）细胞。MHC Ⅰ类链相关蛋白 A 和 B（分别为 MICA 和 MICB）是 NKG2D 的配体，在多种人类肿瘤细胞上表达，包括肝细胞癌（HCC）细胞。在这里，我们研究了化疗药物吉西他滨是否会影响 HCC 中 MICA/B 的表达。
我们使用 ELISA、RT-PCR 和贴壁靶细胞脱落测定法来确定 HepG2 HCC 细胞中 MICA/B 的表达以及吉西他滨和/或 CAK 细胞处理产生的细胞毒性水平。
吉西他滨处理后可观察到 MICA/B 的表面表达，MICB 特异性 mRNA 上调。与单独处理相比，吉西他滨预处理后再暴露于 CAK 细胞可诱导更强的细胞毒性。加入可溶性 MICB 可显著降低细胞毒性。
吉西他滨诱导 HepG2 细胞中 MICA/B 的表达，导致 NKG2D 高表达的 CAK 细胞的细胞毒性协同增强。吉西他滨和 CAK 细胞的联合应用可能对 HCC 具有临床治疗意义。
