地西他滨联合阿霉素对TP53突变弥漫大B淋巴瘤细胞株的影响及临床意义研究  

Effect of decitabine combined with adriamycin on TP53 mutated diffuse large B lymphoma cell line and its clinical significance

作　　者：郑艳丽 贺建霞[1,2] 白斯君 耿晔[1,2] 高轶男 张彩霞[1,2] ZHENG Yanli;HE Jianxia;BAI Sijun;GENG Ye;GAO Yinan;ZHANG Caixia(The Fifth Clinical Medical College of Shanxi Medical University,Taiyuan,030012,China;Department of Hematology,Shanxi Provincial People's Hospital)

机构地区：[1]山西医科大学第五临床医学院,太原030012 [2]山西省人民医院血液科

出　　处：《临床血液学杂志》2024年第1期56-61,共6页Journal of Clinical Hematology

基　　金：山西省自然科学基金(No:201901D111435)。

摘　　要：目的:观察地西他滨对TP53突变弥漫大B细胞淋巴瘤(diffuse large B cell lymphoma,DLBCL)细胞株DB增殖、凋亡及周期的影响,并评估地西他滨联合治疗TP53突变DLBCL患者的疗效及安全性。方法:体外培养细胞,不同浓度(5~80μmol/L)地西他滨和阿霉素作用于DB细胞后采用CCK-8法计算增殖抑制率;地西他滨(20μmol/L)和阿霉素(12μmol/L)作用于DB细胞24/48 h,采用Annexin V-FITC/PI及流式细胞术检测凋亡率及细胞周期;比较不同组间细胞增殖、凋亡及周期的差异。另收集5例地西他滨联合治疗TP53突变DLBCL患者的临床资料进行回顾性总结。结果:对DB细胞的增殖抑制作用随着地西他滨浓度的增加(5、10、20、40、80μmol/L)而增强,联合阿霉素(12μmol/L)后抑制率较单药明显增大[(78.51±1.19)%vs(40.80±1.62)%,(87.48±0.29)%vs(46.83±1.47)%,(92.59±0.15)%vs(47.07±1.50)%,(94.57±0.58)%vs(52.68±0.84)%,(95.56±0.53)%vs(54.95±1.07)%,P<0.01];采用IC50浓度(20μmol/L地西他滨、12μmol/L阿霉素)药物处理细胞,抑制率随时间增加(12、24、48 h)而增大[(50.40±0.19)%、(61.65±0.16)%、(85.08±0.78)%,P<0.01]。与空白对照组比较,地西他滨作用于DB细胞24 h显示S期细胞比例增加[(10.54±0.40)%vs(2.03±0.01)%,P<0.01],48 h显示G2/M期细胞比例增加[(17.45±0.19)%vs(3.69±0.09)%,P<0.01]。5例复发/难治TP53突变DLBCL患者使用含有地西他滨方案治疗后,总有效率为40%(2/5),主要不良反应为骨髓抑制,未出现治疗相关死亡。结论:地西他滨可增强阿霉素对TP53突变DLBCL细胞株的增殖抑制作用,阻滞细胞周期。含地西他滨方案治疗TP53突变DLBCL显示出一定疗效,安全性良好,值得进一步探索。Objective To observe the effect of decitabine(DAC)on the proliferation,apoptosis and cell cycle of TP53 mutated diffuse large B cell lymphoma(DLBCL)cell line DB,and evaluate the efficacy and safety of DAC combined therapy in patients with TP53 mutant DLBCL.Methods Cells were cultured in vitro.The different concentrations(5-80μmol/L)of DAC and adriamycin(ADM)act on DB cells and the CCK-8 method was used to calculate the proliferation inhibition rate.DAC(20μmol/L)and ADM(12μmol/L)act on DB cells 24,48 h,Annexin V-FITC/PI and flow cytometry were used to detect the apoptosis rate and cell cycle.The differences in cell proliferation,apoptosis and cell cycle in different groups were compared.Clinical data of 5 patients with TP53 mutated DLBCL treated with DAC combination was retrospectively collected and summarized.Results The inhibitory effect on the proliferation of DB cells increased with the increase of DAC concentration(5,10,20,40,80μmol/L),and the inhibition rate in combination with ADM(12μmol/L)was significantly higher than that of single drug([78.51±1.19]%vs[40.80±1.62]%,[87.48±0.29]%vs[46.83±1.47]%,[92.59±0.15]%vs[47.07±1.50]%,[94.57±0.58]%vs[52.68±0.84]%,[95.56±0.53]%vs[54.95±1.07]%,P<0.01).When the cells were treated with IC50(20μmol/L DAC,12μmol/L ADM),the inhibition rate increased([50.40±0.19]%,[61.65±0.16]%,[85.08±0.78]%)with the increase of time(12,24,48 h)(P<0.01).Compared with the blank control group,the percentage of DB cells in S phase increased after treatment with DAC for 24 h([10.54±0.40]%vs[2.03±0.01]%,P<0.01),and the proportion of cells in G2/M phase increased at 48 h([17.45±0.19]%vs[3.69±0.09]%,P<0.01).The five patients with recurrent refractory TP53 mutation DLBCL treated with DAC regimen,the total effective rate was 40%(2/5).The main adverse event was myelosuppression and there was no treatment-related death.Conclusion DAC can enhance the inhibitory effect of ADM on the proliferation of TP53 mutant DLBCL cell line,and block cell cycle.The regimen containing DAC shows a

关 键 词：弥漫大B细胞淋巴瘤 复发/难治 TP53突变 阿霉素 地西他滨 

分 类 号：R733.4[医药卫生—肿瘤]