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

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MHC Ⅰ类链相关分子A(major histocompatibility complex class Ⅰ chainrelated 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.

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

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.