Mechanism of <italic style="font-style: italic">Compound Zhebei Granules</italic> in regulating MHC-Ⅱ to reverse multidrug resistance in leukemia through MDM2/p53 signaling pathway

YANG Qianru; TIAN Shaodan; XUE Chengyuan; LI Guangda; ZHANG Yayue; ZHANG Yu; LI Dongyun; QI Yubo; HOU Li

doi:10.16025/j.1674-1307.2025.03.012

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

更新时间：2025-04-29

- Mechanism of Compound Zhebei Granules in regulating MHC-Ⅱ to reverse multidrug resistance in leukemia through MDM2/p53 signaling pathway
- Beijing Journal of Traditional Chinese Medicine Vol. 44, Issue 3, Pages: 325-330(2025)
- 作者机构：
  
  北京中医药大学东直门医院血液肿瘤科，北京 100700
- 作者简介：
- 基金信息：
- DOI：10.16025/j.1674-1307.2025.03.012
  CLC：
- Received：30 June 2024，
  
  Published：25 March 2025
- 稿件说明：
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杨茜茹，田劭丹，薛程元，等.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［J］.北京中医药，2025，44（3）：325-330.

YANG Qianru,TIAN Shaodan,XUE Chengyuan,et al.Mechanism of Compound Zhebei Granules in regulating MHC-Ⅱ to reverse multidrug resistance in leukemia through MDM2/p53 signaling pathway[J]. Beijing Journal of Traditional Chinese Medicine,2025,44(03):325-330.
杨茜茹，田劭丹，薛程元，等.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［J］.北京中医药，2025，44（3）：325-330. DOI： 10.16025/j.1674-1307.2025.03.012.

YANG Qianru,TIAN Shaodan,XUE Chengyuan,et al.Mechanism of Compound Zhebei Granules in regulating MHC-Ⅱ to reverse multidrug resistance in leukemia through MDM2/p53 signaling pathway[J]. Beijing Journal of Traditional Chinese Medicine,2025,44(03):325-330. DOI： 10.16025/j.1674-1307.2025.03.012.

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（IC

）为（2.276±0.218）、（1.254±0.104）、（1.040±0.108）mg/mL，对MOLM-13细胞的IC

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（

0.05），p53蛋白相对表达量高（

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（

0.05），p53蛋白相对表达量高（

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（

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。

Abstract

Objective

To investigate the mechanism by which

Compound Zhebei Granules

（CZBG） reverse multidrug resistance in leukemia by regulating major histocompatibility complex class Ⅱ （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-Ⅱ surface 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 cell

s 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 （

0.05）， while the relative expression of p53 protein was significantly higher （

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 （

0.05）. After 24 hours of CZBG treatment， MHC-Ⅱ surface expression was significantly increased in both KG-1a and MOLM-13 cells （

0.05）.

Conclusion

The mechanism of CZBG in reversing multidrug resistance in leukemia may be related to regulating the expression of MHC-Ⅱ on the surface of leukemia cells through the MDM2/p53 pathway and thereby interfering with immune evasion.

关键词

Keywords

references

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

DOI：10.16025/j.1674-1307.2025.03.012

摘要

Abstract

关键词

Keywords

references