三氧化二砷提高多发性骨髓瘤ARH-77细胞对NK细胞杀伤敏感性的研究

Effects of arsenic trioxide on NK cell cytotoxicity against multiple myeloma cell lines ARH-77

目的研究三氧化二砷(arsenic trioxide,ATO)前后人多发性骨髓瘤ARH-77对NK细胞杀伤细胞敏感性的变化,并初步探讨其机制。方法分别应用CCK-8法和台盼蓝染色法测算ATO对ARH-77细胞株的50%抑制量(IC50)和细胞活性;乳酸脱氢酶释放法检测ATO作用前后ARH-77细胞对NK细胞的杀伤敏感性。流式细胞仪检测ARH-77细胞表面NKG2D配体(MICA/B、ULBP1、ULBP2、ULBP3)和HLA-Ⅰ类分子表达以及ATO作用前后的细胞周期变化。结果ATO对ARH-77细胞的IC50为5.0μmol/L。NK细胞杀伤ATO作用前后ARH-77细胞的活性有显著差异(P<0.05)。ATO作用后,ARH-77细胞发生G1/S期阻滞,同时其表面MICA/B、ULBP1、ULBP3表达显著升高,二者之间差异有统计学意义(P<0.05)。ULBP2和HLA-Ⅰ类分子无明显变化(P>0.05)。结论ATO能提高ARH-77细胞NKG2D配体(MICA/B、ULBP1、ULBP3)表达;从而使其对NK细胞的杀伤敏感性增强。

Objective To explore the effects of arsenic trioxide(ATO)on NK cell cytotoxicity against multiple myeloma cell lines ARH-77.Methods The IC50 and survival rates of ARH-77 cells treated by 2.5,5.0,10 μmol/L ATO for 24,48,96 h were measured by cck-8 assay and trypanblau staining method,respectively.Cytotoxicities against ARH-77 cell of NK cells isolated from 3 healthy volunteers were analyzed by LDH releasing assay at different effector-to-target cell ratios(E:T)before and after treated by ATO.The expressions ...