摘要: |
[摘要]目的:探讨盐酸小檗碱(BBR)增敏柔红霉素(DNR)诱导儿童急性淋巴细胞白血病原代细胞(P-ALLCs)凋亡的作用及相关机制。方法:收集初诊初治的急性淋巴细胞白血病(ALL)儿童骨髓标本12例,分离单个核细胞,按活细胞数2×105/mL接种于含20%小牛血清1640的96孔培养板,培养4 h后按照设定DNR 4个浓度和BBR 3个浓度单药及交叉联合应用方案加入不同体积的PBS稀释DNR和BBR储备液培养干预24 h,采用cell counting kit-8 assay(CCK-8)检测DNR和BBR单药作用以及两者联合作用对P-ALLCs增殖的抑制作用。结果:DNR单药作用时抑制率为(11.56%±0.73%)~(59.60%±2.80%),随着DNR浓度的增加,P-ALLCs的增殖抑制逐渐增强,且后一浓度与前一浓度比较差异均有统计学意义(P均<0.05);BBR单药作用时抑制率为(12.39%±1.50%)~(39.75%±2.43%),随着BBR浓度的增加,P-ALLCs的增殖抑制逐渐增强,且后一浓度与前一浓度比较差异均有统计学意义(P均<0.05);DNR联合BBR时的抑制率为(18.43%±1.11%)~(89.96%±1.40%)。在4个联合用药组中,随着BBR浓度的增加,对P-ALLCs的增殖抑制逐渐增强(P均<0.05),而且每一组中DNR联合BBR后的抑制率比DNR单药作用强(P均<0.05)。结论:DNR和BBR对儿童P-ALLCs均有细胞毒性作用并成浓度依赖性。 两药联合作用时BBR可以增加儿童急性淋巴细胞白血病原代细胞对DNR的敏感性,该作用与浓度有一定的相关性。 |
关键词: 儿童 急性淋巴细胞白血病 原代细胞 盐酸小檗碱 柔红霉素 凋亡 |
DOI:doi:10.13407/j.cnki.jpp.1672-108X.2020.01.001 |
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基金项目:湖北省科技厅面上项目,编号 2012FFB05302;武汉市卫生计生委临床研究课题项目,编号 WX13B19。 |
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Effects of Berberine Enhance on Daunorubicin-Induced Apoptosis of Primary Acute Lymphoblastic Leukemia Cells in Children |
Yang Li1, Li Jiaojiao2, Cheng Yanyang2, Lu Wenjie1, Wang Zhuo1, Tao Fang1, Nie Yingming1, Fan Jing1, Li Jianxin1, Xiong Hao1 |
(1. Wuhan Children’s Hospital of Tongji Medical College of Huazhong University of Science and Technology, Hubei Wuhan 430016, China; 2. Renmin Hospital of Wuhan University, Hubei Wuhan 430060, China) |
Abstract: |
[Abstract] Objective: To probe into the effects of berberine (BBR) enhance on daunorubicin (DNR)-induced apoptosis of primary acute lymphoblastic leukemia cells (P-ALLCs) in children and the related mechanism. Methods: Bone marrow samples were collected from 12 children newly diagnosed with acute lymphoblastic leukemia (ALL), mononuclear cells were isolated, 2×105/mL living cells was inoculated in the 96-well culture plate containing 20% calf serum 1640. After culture for 4 h, different volumes of PBS were added to dilute DNR and BBR stock solutions according to the single drug and cross-combination application scheme of concentration of 4 DNR and 3 BBR for 24 h of culture intervention. Cell counting kit-8 assay (CCK-8) was used to detect the single drug effects of DNR and BBR and the combination effects on the inhibition of P-ALLCs proliferation. Results: The inhibition rate of DNR was (11.56%±0.73%) to (59.60%±2.80%), with the increase of DNR concentration, the proliferation inhibition of P-ALLCs increased, and the difference between the latter concentration and the previous concentration was statistically significant (P<0.05). The inhibition rate of BBR was (12.39%±1.50%) to (39.75%±2.43%), with the increase of BBR concentration, the proliferation inhibition of P-ALLCs increased, and the difference between the latter concentration and the previous concentration was statistically significant (P<0.05). The inhibition rate of DNR combined with BBR was (18.43%±1.11%) to (89.96%±1.40%). In the four combined groups, the proliferation inhibition of P-ALLCs increased with the increase of BBR concentration (P<0.05), and the inhibition rate of DNR combined with BBR in each group was stronger than that of DNR alone (P<0.05). Conclusion: Both DNR and BBR shows cytotoxic effects and concentration dependence on P-ALLCs in children. BBR can increase the sensitivity of P-ALLCs to DNR, and the effect is related to the concentration. |
Key words: children acute lymphoblastic leukemia, primary cells berbeine, daunorubicin, apoptosis |