吉林大学学报(医学版)

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冬凌草甲素协同马法兰对人骨髓瘤RPMI-8226细胞增殖和凋亡的影响

郝亚宁1，罗媛媛2，张梅2，李莎莎1   

  1. 1.西安交通大学医学院第一附属医院肾内科， 陕西 西安 710061；2. 西安交通大学医学院第一附属医院血液内科， 陕西 西安 710061
  • 收稿日期:2012-11-27 出版日期:2013-07-28 发布日期:2013-08-17
  • 通讯作者: 郝亚宁（Tel: 029-85323950,E-mail: haoynhaoyn@163.com） E-mail:haoynhaoyn@163.com
  • 作者简介:郝亚宁(1964-)，女，陕西省西安市人，副教授，医学硕士，主要从事慢性肾脏病、骨髓瘤肾病发生机制及防治研究。
  • 基金资助:

    陕西省科技厅科技攻关项目资助课题 (2008K09-09)

Influence of oridonin combined with melphalan on proliferation and apoptosis of human myeloma RPMI8226 cells

HAO Ya-ning1,LUO Yuan-yuan2,ZHANG Mei2,LI Sha-sha1   

  1. 1. Department of Nephrology,First Affiliated Hospital,School of Medical Sciences,Xi’an Jiaotong University,Xi’an 710061,China;2. Department of Heamotology,First Affiliated Hospital,Schoolof Medical Sciences,Xi’an Jiaotong University,Xi’an 710061,China
  • Received:2012-11-27 Online:2013-07-28 Published:2013-08-17

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摘要：

目的: 观察冬凌草甲素（oridonin）和马法兰( melphalan)单药及联合用药对人骨髓瘤RPMI-8226细胞生长、凋亡和细胞周期的影响及二者的协同作用，阐明药物联合应用对骨髓瘤细胞的毒性增强作用。方法: 本实验共设4个RPMI-8226细胞处理组，即空白对照组（未加任何药物）、冬凌草甲素（10  μmol/L）组、马法兰（30  μmol/L）组和联合（冬凌草甲素 10  μmol/L + 马法兰 30  μmol/L）组。MTT法检测各用药组作用不同时间后RPMI-8226细胞的增殖抑制率，采用两药相互作用指数（CDI）评价联合用药性质；Annexin-Ⅴ/PI双染检测细胞凋亡率；流式细胞术检测药物作用前后细胞周期分布。结果:与空白对照组比较，冬凌草甲素组、马法兰组和联合组RPMI-8226细胞增殖抑制率明显增加(P<0.01)，均具有时间-效应依赖性，联合组各时间点细胞增殖抑制率明显高于单药组(P<0.01)。各时间点CDI值均小于1，即冬凌草甲素可协同提高马法兰的细胞毒作用。冬凌草甲素和马法兰单独处理RPMI-8226细胞36 h，细胞凋亡率分别为15.01%±0.47％ 和20.03%±1.30％，而联合组细胞凋亡率为43.06%±1.96％，与单药组比较显著升高(P<0.01)。流式细胞术DNA含量分析，各药物组RPMI-8226细胞主要阻滞于G0/G1期，S期细胞比例明显减少，除冬凌草甲素组S期细胞比例外，其余药物组各期细胞比例与空白对照组比较差异均有统计学意义(P<0.05或P<0.01)，联合组与单药组比较差异亦有统计学意义(P<0.01)。结论: 冬凌草甲素联合马法兰通过阻滞细胞周期和诱导细胞凋亡而抑制骨髓瘤细胞的增殖，其作用具有协同性。

关键词: 骨髓瘤细胞, 冬凌草甲素, 马法兰, 细胞凋亡, 细胞周期, 协同作用

Abstract:

Abstract:Objective To investigate the influence of oridonin combined with melphalan in cell proliferation,apoptosis and cell cycle of myeloma RPMI8226 cells and their synergistic effect,and to clarify the cytotoxin enhanced effect of the combination of the two drugs on myeloma cells. Methods The RPMI-8226 cells were divided into blank  control group,oridonin（10  μmol/L）　group,melphalan（30  μmol/L）group and oridonin(10 μmol/L) + melphalan(30 μmol/L) group.The inhibitory rates of proliferation of RPMI-8226 cells were detected by MTT assay after treated with oridonin,melphalan alone or in  combination  at different time.The drug synergistic effect was expressed by coefficient of drug interaction (CDI).The change of cell cycle was analyzed by flow cytometry,and the apoptotic rate was detected by Annexin-Ⅴ/PI staining.Results Compared with blank control group,the inhibitory rates of proliferation of RPMI-8226 in oridonin,melphalan and oridonin+melphalan group were significantly increased(P<0.01) in a time-dependent manner.Compared with single drug groups,the inhibitory rates in oridonin+melphalan group at different time were significantly increased (P<0.01).The CDI values of two drugs at different time were less than 1,which indicated that oridonin could improve the cytotoxicity of melphalan.The apoptotic rate of combination use of two drugs was 43.06%±1.96％,which was significantly higher than single oridonin (15.01%±0.47％) and melphalan (20.03%±1.30％) (P<0.01).Flow cytometry DNA analysis showed that oridonin,melphalan or combination use could induce the arrest of most RPMI-8226 cells at G0/G1 phase,the ratio of RPMI-8226 cells at  S phase was reduced,there was significant difference between drug groups and blank control group (P<0.01),and there also was significant difference between oridonin+melphalan  group and  single drug  groups (P<0.01).Conclusion Oridonin combined with melphalan can synergisticly inhibit the proliferation of RPMI-8226 myeloma cells by arresting cell cycle and inducing apoptosis.

Key words: myeloma cells；oridonin；melphalan；apoptosis；cell cycle; , synergistic effect

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