复方浙贝颗粒基于MDM2/p53信号通路调节MHC-Ⅱ逆转白血病多药耐药机制研究  

Mechanism of Compound Zhebei Granules in regulating MHC-Ⅱto reverse multidrug resistance in leukemia through MDM2/p53 signaling pathway

作　　者：杨茜茹 田劭丹[1] 薛程元 李光达 张雅月[1] 张宇[1] 李冬云[1] 齐宇镈 侯丽[1] YANG Qianru;TIAN Shaodan;XUE Chengyuan;LI Guangda;ZHANG Yayue;ZHANG Yu;LI Dongyun;QI Yubo;HOU Li(Department of Hematology and Oncology,Dongzhimen Hospital,Beijing University of Chinese Medicine,Beijing 100700,China)

机构地区：[1]北京中医药大学东直门医院血液肿瘤科,北京100700

出　　处：《北京中医药》2025年第3期325-330,共6页Beijing Journal of Traditional Chinese Medicine

基　　金：北京市自然科学基金项目(7242236);国家自然科学基金资助项目(82074240);国家中医药管理局高水平中医药重点学科建设项目(zyyzdxk-2023268);北京市科技计划课题十病十药研发项目(Z151100003815027)。

摘　　要：目的 探讨复方浙贝颗粒(CZBG)基于双微体同源基因2(MDM2)/p53信号通路调节主要组织相容性复合体Ⅱ类(MHC-Ⅱ)逆转白血病多药耐药的作用机制。方法 选取人急性髓系白血病细胞(KG-1a、MOLM-13细胞),将KG-1a、MOLM-13细胞分别分为CZBG组、空白对照组。空白对照组予完全培养基培养,CZBG组予含不同浓度的CZBG完全培养基培养。CCK-8法检测细胞增殖,Western blotting法检测MDM2、p53蛋白表达,流式细胞术检测MHC-Ⅱ表达。结果 干预24、48、72 h,CZBG对KG-1a、MOLM-13细胞增殖均具有抑制作用。其中CZBG在24、48、72 h时对KG-1a细胞的半数抑制浓度(IC50)为(2.276±0.218)、(1.254±0.104)、(1.040±0.108)mg/mL,对MOLM-13细胞的IC50为(2.809±0.121)、(1.585±0.103)、(1.194±0.105)mg/mL。应用2.2 mg/mL CZBG干预KG-1a细胞24 h时,与空白对照组比较,CZBG组MDM2蛋白相对表达量低(P<0.05),p53蛋白相对表达量高(P<0.05)。用2.8 mg/mL CZBG干预MOLM-13细胞24 h时,与空白对照组比较,CZBG组MDM2蛋白表达低(P<0.05),p53蛋白相对表达量高(P<0.05)。KG-1a、MOLM-13细胞分别经CZBG处理24 h,CZBG组细胞表面的MHC-Ⅱ表达高(P<0.05)。结论 CZBG逆转白血病多药耐药的作用机制可能与通过MDM2/p53通路调节白血病细胞表面MHC-Ⅱ表达,干预免疫逃逸有关。Objective To investigate the mechanism by which Compound Zhebei Granules(CZBG)reverse multidrug resistance in leukemia by regulating major histocompatibility complex classⅡ(MHC-Ⅱ)expression through the murine double minute 2(MDM2)/p53 signaling pathway.Methods Human acute myeloid leukemia cell lines KG-1a and MOLM-13 were selected and divided into a CZBG group and a blank control group.The control group was cultured in complete medium,while the CZBG group was cultured in complete medium containing different concentrations of CZBG.Cell proliferation was assessed using the CCK-8 assay.The expression levels of MDM2 and p53 proteins were detected by Western blotting,and MHC-Ⅱsurface expression was measured by flow cytometry.Results At 24,48,and 72 hours of intervention,CZBG inhibited the proliferation of KG-1a and MOLM-13 cells.The half-maximal inhibitory concentrations(IC50)of CZBG against KG-1a cells at 24,48,and 72 hours were(2.276±0.218),(1.254±0.104),and(1.040±0.108)mg/mL,respectively.The IC50 values for MOLM-13 cells were(2.809±0.121),(1.585±0.103),and(1.194±0.105)mg/mL,respectively.After 24 hours of treatment with 2.2 mg/mL CZBG,the relative expression of MDM2 protein in KG-1a cells was significantly lower than that in the control group(P<0.05),while the relative expression of p53 protein was significantly higher(P<0.05).Similarly,treatment of MOLM-13 cells with 2.8 mg/mL CZBG for 24 hours resulted in significantly decreased MDM2 protein expression and increased p53 protein expression compared to the control group(P<0.05).After 24 hours of CZBG treatment,MHC-Ⅱsurface expression was significantly increased in both KG-1a and MOLM-13 cells(P<0.05).Conclusion The mechanism of CZBG in reversing multidrug resistance in leukemia may be related to regulating the expression of MHC-Ⅱon the surface of leukemia cells through the MDM2/p53 pathway and thereby interfering with immune evasion.

关 键 词：复方浙贝颗粒 双微体同源基因2(MDM2)/p53信号通路 主要组织相容性复合体Ⅱ类 白血病 多药耐药 作用机制 

分 类 号：R285.5[医药卫生—中药学]