北京中医药2025，Vol.44Issue(7)：820-826,7.DOI:10.16025/j.1674-1307.2025.07.002
复方黄黛片组方配伍逆转急性早幼粒细胞白血病小鼠砷剂耐药的机制研究
Mechanisms of Compound Huangdai Tablet Formulation in reversing arsenic resistance in mice with acute promyelocytic leukemia
摘要
Abstract
Objective To clarify the antitumor effects and mechanisms of Compound Huangdai Tablet formulation in reversing arsenic resistance in HL-60-promyelocytic leukemia(PML)A216V-retinoic acid receptor α(RARα)tumor-bearing mice.Methods A xenograft model was established in nude mice using arsenic-resistant HL-60-PMLA216V-RARα cells.After model establishment,the mice were randomly divided into model group,realgar group,three-drug combination group,and four-drug combination group,with five mice in each group.Mice were gavaged with normal saline or water decoctions of the corresponding drugs.Body weight and tumor volume were recorded during the experiment,and tumor tissues were collected after 2 weeks.Pathological morphology was observed by HE staining,apoptosis was detected by TUNEL assay,Ki-67 expression was assessed by immunohistochemistry,and CD33 and CD11b expression levels were measured by flow cytometry.Results Tumor volumes in the three-drug and four-drug combination groups were significantly smaller than those in the model and realgar groups(P<0.01).Tumor volume in the realgar group was lower than that in the model group,but the difference was not statistically significant(P>0.05).Tumor weights in the three-drug and four-drug groups did not differ significantly from that in the realgar group(P>0.05).Tumor inhibition rates were 21.93%in the realgar group,37.77%in the three-drug group,and 43.60%in the four-drug group.Histologically,tumors in the realgar group showed relatively loose cell arrangement with pericellular vacuoles;the three-drug group exhibited markedly loose structures with abundant fat vacuoles;the four-drug group displayed more disorganized structures with abundant fat vacuoles.Compared with the realgar group,the apoptosis rate was lower in the three-drug group(P<0.01)and higher in the four-drug group(P<0.01).Compared with the three-drug group,the apoptosis rate in the four-drug group was also higher(P<0.01).The proportion of Ki-67 positive cells was higher in the three-drug group than in the realgar group(P<0.01),and lower in the four-drug group than in the three-drug group(P<0.01).Compared with the realgar group,CD33 expression was reduced in the three-drug group(P<0.01)but elevated in the four-drug group relative to the three-drug group(P<0.01).CD11b expression showed a downward trend in the three-drug group compared with the realgar group,though not statistically significant(P>0.05),while it was significantly increased in the four-drug group(P<0.01),with a significant difference also observed between the three-and four-drug groups(P<0.01).Conclusion The Compound Huangdai Tablet formulation exerts pro-apoptotic and differentiation-inducing effects,and inhibits proliferation in arsenic-resistant acute promyelocytic leukemia(APL)cells,thereby contributing to the reversal of arsenic resistance.关键词
复方黄黛片/急性早幼粒细胞白血病/砷剂耐药/细胞凋亡/细胞分化Key words
Compound Huangdai Tablet/acute promyelocytic leukemia(APL)/arsenic resistance/cell apoptosis/cell differentiation引用本文复制引用
薛程元,侯丽,崔美晨,文旭,廖镜林,齐宇镈,司雨平,杨茜茹,韩欣璞,刘可心..复方黄黛片组方配伍逆转急性早幼粒细胞白血病小鼠砷剂耐药的机制研究[J].北京中医药,2025,44(7):820-826,7.基金项目
国家自然科学基金项目(82074240) （82074240）
中央高水平中医医院临床科研业务费项目(CZ015) （CZ015）
国家中医药管理局高水平重点学科中医血液学建设项目(zyyzdxk-2023268) （zyyzdxk-2023268）
