CAJ | 학술논문

目的:研究表皮生长因子受体酪氨酸激酶抑制剂厄洛替尼对人肺腺癌A549细胞NKG2D配体表达及CIK细胞杀伤活性的影响及其分子机制.方法:流式细胞仪检测厄洛替尼、EGFR下游分子LY294002(PI3K抑制剂)、SB203580(MAPK抑制剂)、STAT21(STAT3抑制剂)作用A549细胞24 h后A549细胞NKG2D配体的表达.乳酸脱氢酶释放法测定不同效靶比时,CIK细胞对10μmol/L厄洛替尼作用前、后A549细胞的杀伤活性.结果:厄洛替尼下调A549细胞MICA表达,上调MICB、ULBP1表达,EGFR下游分子MAPK、STAT3抑制剂不影响A549细胞NKG2D配体的表达,PI3-K抑制剂下调A549细胞MICA表达,厄洛替尼增强A549细胞对CIK细胞杀伤的敏感性.结论:EGFR TKI抗肺癌作用与其增强肺癌细胞对免疫细胞杀伤的敏感性有关.
목적:연구표피생장인자수체락안산격매억제제액락체니대인폐선암A549세포NKG2D배체표체급CIK세포살상활성적영향급기분자궤제.방법:류식세포의검측액락체니、EGFR하유분자LY294002(PI3K억제제)、SB203580(MAPK억제제)、STAT21(STAT3억제제)작용A549세포24 h후A549세포NKG2D배체적표체.유산탈경매석방법측정불동효파비시,CIK세포대10μmol/L액락체니작용전、후A549세포적살상활성.결과:액락체니하조A549세포MICA표체,상조MICB、ULBP1표체,EGFR하유분자MAPK、STAT3억제제불영향A549세포NKG2D배체적표체,PI3-K억제제하조A549세포MICA표체,액락체니증강A549세포대CIK세포살상적민감성.결론:EGFR TKI항폐암작용여기증강폐암세포대면역세포살상적민감성유관.
Objective:This study aims to explore the effects of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) on the expression of natural killer group 2, member D receptor (NKG2D) ligands in human lung cancer A549 cells and on the cy-totoxicity mediated by cytokine-induced killer (CIK) cells. Methods:The expression of NKG2D ligands (i.e., major histocompatibility complex class I chain-related molecules A or B (MICA, MICB), up-regulation of UL16-binding protein (ULBP)1, ULBP2, and ULBP3) on A549 cells were analyzed before and after treatment with erlotinib, phosphatidylinositol 3-kinase (PI3-K) selective inhibi-tors, mitogen-activated protein kinases (MAPK), and signal transducers and activators of transcription 3 (STAT3). The cytotoxicities of CIK cells against A549 cells before and after treatment with 10μmol/L of erlotinib were detected by lactate dehydrogenase releasing as-say at 10∶1, 20∶1, and 30∶1 effect-to-target cell ratios. Results:After treatment with 5 or 10μmol/L of erlotinib, the MICB and ULBP1 expressions on A549 cells increased, whereas the MICA expression decreased (P<0.05). Minimal changes were observed on ULBP2 and ULBP3 (P>0.05). The inhibitors of EGFR downstream molecules, namely, MAPK inhibitors (SB203580) and STAT3 inhibitors (STAT21), had no effect on the expression of NKG2D ligands, whereas the PI3-K inhibitors (LY294002) decreased the MICA expres-sion. The cytotoxicity of CIK cells against A549 cells treated with 10μmol/L of erlotinib was significantly enhanced (P<0.05). Conclu-sion: Results indicate that the therapeutic efficacy of EGFR TKI in lung cancer may be mediated by increasing the susceptibility of cells to immune-cell-mediated cytotoxicity. Therefore, combination therapies with erlotinib and CIK cells may have clinical therapeutic significance for lung cancer patients.