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双黄升白颗粒对化疗所致骨髓抑制Lewis肺癌荷瘤小鼠细胞周期的双重调控作用及其机制
引用本文:王立芳,徐振晔,金长娟,沙慧芳,王中奇,周卫东,张铭,吴继,白冰.双黄升白颗粒对化疗所致骨髓抑制Lewis肺癌荷瘤小鼠细胞周期的双重调控作用及其机制[J].中西医结合学报,2009,7(5):453-457.
作者姓名:王立芳  徐振晔  金长娟  沙慧芳  王中奇  周卫东  张铭  吴继  白冰
作者单位:1. 上海中医药大学中医肿瘤研究所,上海,200032
2. 上海交通大学胸科医院肿瘤研究室,上海,200030
摘    要:目的:探讨双黄升白颗粒对化疗所致骨髓抑制荷瘤小鼠骨髓和肿瘤细胞周期双重调控的作用机制。 方法:本研究采用Lewis肺癌荷瘤小鼠,30只小鼠随机分为空白组、模型组和治疗组。除空白组外,腹腔注射环磷酰胺制作骨髓抑制模型。治疗组用40g/(kg·d)双黄升白颗粒治疗6d后,流式细胞仪检测细胞周期情况,并计算增殖指数(proliferationindex,PI);蛋白印迹法和免疫组织化学法检测骨髓及肿瘤组织中细胞周期蛋白依赖激酶4(cyclin-dependent kinase4,CDK4)、细胞周期蛋白依赖激酶6(cyclin-dependent ki-nase6,CDK6)和细胞周期蛋白D1(cyclin D1)的表达。 结果:模型组骨髓及肿瘤的G0/G1期细胞比例均低于空白组(P〈0.05),PI和CDK4、CDK6、cyclin D1表达高于空白组(P〈0.05)。治疗组骨髓G0/G1期细胞比例低于模型组及空白组,PI及CDK4、CDK6、cyclinD1表达均高于模型组及空白组;肿瘤组织G0/G1期细胞比例高于模型组及空白组,PI及CDK4、CDK6、cyc-lin D1表达均低于模型组及空白组。 结论:双黄升白颗粒对骨髓抑制Lewis肺癌荷瘤鼠的细胞周期具有双重调控作用,其机制可能与双重调节cyclin D1、CDK4和CDK6表达有关。

关 键 词:双黄升白颗粒  细胞周期  双重调控    Lewis肺  细胞周期蛋白D1  细胞周期蛋白依赖激酶类  小鼠

Dual regulation of cell cycles by Shuanghuang Shengbai Granule in Lewisbearing mice with chemotherapy-induced myelosuppression and its mechanism
Li-fang WANG,Zhen-ye XU,Chang-juan JIN,Hui-fang SHA,Zhong-qi WANG,Wei-dong ZHOU,Ming ZHANG,Ji WU,Bing BAI.Dual regulation of cell cycles by Shuanghuang Shengbai Granule in Lewisbearing mice with chemotherapy-induced myelosuppression and its mechanism[J].Journal of Chinese Integrative Medicine,2009,7(5):453-457.
Authors:Li-fang WANG  Zhen-ye XU  Chang-juan JIN  Hui-fang SHA  Zhong-qi WANG  Wei-dong ZHOU  Ming ZHANG  Ji WU  Bing BAI
Institution:1. Cancer Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China; 2. Division of Cancer Research, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, China)
Abstract:Objective: To explore the dual regulatory effects of Shuanghuang Shengbai Granule, a compound traditional Chinese herbal medicine, on cell cycle in Lewis-bearing mice with chemotherapy-induced myelosuppression.
Methods: Thrity Lewis-bearing mice were randomly divided into control group, untreated group and treated group. A model of myelosuppression was established by peritoneal injection of cyclophosphamide to Lewisbearing mice. Mice in the treated group were treated with Shuanghaung Shengbai Granule for 6 days. Cell cycle progressions of cells collected from bone marrow and tumor tissues were assayed by flow cytometry, and proliferation index (PI) was also calculated. Expressions of cyclin-dependent kinase 4 (CDK4), cyclindependent kinase 6 (CDK6) and cyclin D1 in bone marrow and tumor tissues were detected by Western blotting and immunohistochemical method. Results. Percentages of bone marrow and tumor cells in G0/G1 phase in the untreated group were lower than those in the control group; however, the PI of untreated group was higher than that of the control group. The expressions of CDK4, CDK6 and cyclin D1 in bone marrow and tumor tissues in the untreated group were increased as compared with the control group. Compared with the untreated group and the control group, the percentage of bone marrow cells in G0/G1 phase was decreased, and the PI of bone marrow cells and the expressions of CDK4, CDK6 and cyclin D1 were increased in bone marrow in the treated group. However, the percentage of tumor cells in G0/G1 phase in the treated group was increased, and the PI of tumor cells and the expressions of CDK4, CDK6 and cyciin D1 untreated and control groups. n tumor tissues were decreased as compared with the Conclusion: Shuanghuang Shengbai Granule may have a function of cell cycle dual regulation in Lewis-bearing mice with chemotherapy-induced myelosuppression by regulating the expressions of CDK4, CDK6 and cyclin D1 in bone marrow and tumor tissues.
Keywords:Shuanghuang Shengbai Granule  cell cycle  dual regulations  carcinoma  Lewis lung  cyclin D1  cyclin-dependent kinases  mice
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