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• 基础研究 •    下一篇

20(S)-原人参二醇对荷瘤裸鼠化疗的增效减毒作用

张 锐,徐华丽,于小风,曲绍春,陈明侠,睢大员   

  1. (吉林大学药学院药理学教研室,吉林 长春 130021)
  • 收稿日期:2008-04-02 修回日期:1900-01-01 出版日期:2009-03-28 发布日期:2009-08-14
  • 通讯作者: 睢大员

Enhancing effect of chemotherapy and reducing toxicity of 20(S)-protopanaxadiol on tumor-bearing nude mice

ZHANG Rui,XU Hua-li,YU Xiao-feng,QU Shao-chun,CHEN Ming-xia,SUI Da-yuan   

  1. (Department of Pharmacology,School of Pharmacy,Jilin University,Changchun 130021,China)
  • Received:2008-04-02 Revised:1900-01-01 Online:2009-03-28 Published:2009-08-14
  • Contact: SUI Da-yuan

摘要: 目的:研究20(S)-原人参二醇(Protopanaxadiol,PPD)对环磷酰胺(CTX)化疗人小细胞肺癌荷瘤裸鼠的增效、减毒作用及其机制。方法:建立A549人小细胞肺癌裸鼠体内移植肿瘤模型,随机分为:对照组、PPD组、CTX小剂量组、CTX大剂量组、CTX小剂量+PPD组和CTX大剂量+PPD组,于移植肿瘤模型成功建立后次日起分别腹腔注射0.5%羧甲基纤维素钠、PPD(50 mg•kg-1•d-1)、 CTX(10 mg•kg-1•d-1)、CTX(20 mg•kg-1•d-1)、CTX(10 mg•kg-1•d-1)+PPD(50 mg•kg-1•d-1)和CTX(20 mg•kg-1•d-1)+PPD(50 mg•kg-1•d-1),连续15 d给药后检测小鼠体重、肿瘤重量及体积、外周血白细胞数量、骨髓有核细胞计数、脾脏及胸腺指数、T淋巴细胞转化率、NK细胞杀伤活性,采用流式细胞术检测细胞凋亡情况,同时检测caspase-3活性。结果:与单独化疗药物组比较,PPD(50 mg•kg-1)与化疗药联合组抑瘤率升高(P<0.01),骨髓有核细胞数增加(P<0.01),脾脏及胸腺指数均增高(P<0.01),T淋巴细胞增殖能力和NK细胞杀伤活性均增强(P<0.05)。与单独化疗药物组比较,联合用药组肿瘤细胞凋亡率及caspase-3活性均明显提高(P<0.05或P<0.01),单独使用PPD组caspase-3活性增加不显著。结论:PPD对CTX化疗人小细胞肺癌荷瘤裸鼠有明显的增效、减毒作用,其机制可能与提高机体免疫力、活化caspase-3诱导肿瘤细胞凋亡有关。

关键词: 肺肿瘤, 小鼠, 裸, 环磷酰胺, 增效减毒, 细胞凋亡

Abstract: To observe the enhancing effect and reducing toxicity of 20(S)-protopanaxadiol (PPD) in combination with cyclophosphamide (CTX) on transplanated tumor human lung carcinoma A549 cells.Methods The transplanted tumor models with human lung carcinoma A549 cells were established and then divided randomly into six groups: control group,PPD group,low dose CTX group,high dose CTX group,PPD combined with low dose CTX group and PPD combined with high dose CTX group.The mice in each group were injected intraperitoneally with same amount of CMC,PPD (50 mg•kg-1•d-1),CTX (10 mg•kg-1•d-1),〖JP2〗CTX (20 mg•kg-1•d-1),CTX(10 mg•kg-1•d-1)+PPD (50 mg•kg-1•d-1) and PPD (50 mg•kg-1•d-1)+ CTX (20 mg•kg-1•d-1),respectively.After administration for 15 d,the mice were killed and the mouse weight,tumor weight and volume,the number of WBC in peripheral blood, the count of bone marrow nucleated cells,spleen and thymus indexes,proliferation of T lymphocytes and nature killer cell activity were detected.At the same time,the apoptotic rate and activity of caspase-3 were analyzed by flow cytometry.Results Compared with CTX groups,the inhibitory rate of tumor in PPD(50 mg•kg-1) +CTX group increased (P<0.01),the count of bone marrow nucleated cells increased (P<0.01),the spleen and thymus indexes increased (P<0.01), the proliferation ability of T lymphocytes (P<0.05)and nature killer cell activity increased (P<0.01). Compared with CTX groups,the apoptotic rates(P<0.01) and activities of caspase-3 in PPD+CTX groups increased significantly(P<0.05),but there was no significant difference between PPD and CTX groups.Conclusion PPD could significantly enhance the anti-tumor activity of CTX against lung cancer on nude mice and reduce the side effects simultaneously by up-regulating the activity of caspase-3 and inducing the apoptosis.

Key words: lung neoplasms, mice, nude, cyclophosphamide, enhancing effect and reducing toxicity, apoptosis

中图分类号: 

  • R285