硼替佐米提高耐药K562/ADM细胞对NK细胞杀伤的敏感性及其机制

Bortezomib increases cytotoxic sensitivity of drug-resistant K562 /ADM cells to NK cells and its mechanisms

目的:探讨硼替佐米提高耐药K562/ADM细胞对NK细胞杀伤敏感性的可能机制。方法:流式细胞术和real-time PCR检测硼替佐米处理前后K562/ADM细胞表面MHCⅠ类链相关分子A(major histocompatibility complex classⅠchain-related molecule A,MICA)蛋白和mRNA的表达,LDH释放法检测硼替佐米处理前后K562/ADM细胞对NK细胞的杀伤敏感性。结果:硼替佐米处理后,K562/ADM细胞表面MICA蛋白表达率上升[(17.03±4.94)%vs(23.77±5.26)%,P<0.05];处理后K562/ADM细胞MICA mRNA的表达水平是处理前的(2.03±0.33)倍。效靶比为10∶1、20∶1时,NK细胞对硼替佐米处理后的K562/ADM细胞的杀伤率上升[(23.22±3.03)%、(30.30±0.74)%vs(33.69±1.28)%、(41.40±1.97)%,P<0.05]。结论:硼替佐米提高耐药K562/ADM细胞对NK细胞杀伤的敏感性,其机制可能与硼替佐米上调K562/ADM细胞MICA表达有关。

Objective ： To investigate the effects of bortezomib on the cytotoxic sensitivity of drug-resistant K562/ADM cells to natural killer （NK） cells and the underlying mechanisms. Methods： The expressions of MICA protein and mRNA on K562/ADM target cells before and after incubation with bortezomib were detected by flow cytometry and real-time PCR, respectively. The cytotoxic sensitivity of K562/ADM cells treated with or without bortezomib to NK cells was measured by LDH releasing assay. Results： The expression rates of MICA protein on K562/ADM cells incubated with bortezomib increased from （17.03±4.94）% to （23.77±5.26）% （P〈0.05）. The mRNA expression of MICA on K562/ADM cells treated with bortezomib increased （2.03±0.33） times. At the E∶T ratio of 10∶1 and 20∶1, the cytotoxic sensitivity of K562/ADM cells to NK cells increased from （23.22±3.03）% and （30.30±0.74）% in untreated cells to （33.69±128）% and （41.40±1.97）% in bortezomib-treated cells, respectively, showing significant differences （P〈0.05）. Conclusion： Bortezomib can up-regulate the MICA expression in K562/ADM cells and thus may enhance the cytotoxicity of NK cells against K562/ADM cells.