博落回总碱对肝癌细胞的毒性作用和体内抗肿瘤作用

南方医科大学学报 ›› 2005, Vol. 25 ›› Issue (03): 325-328.

博落回总碱对肝癌细胞的毒性作用和体内抗肿瘤作用

庞建新¹, 马仁强², 刘兰梅³, 蒋毅萍¹, 孙莉莎¹

1. 南方医科大学药理教研室, 广东, 广州, 510515;
2. 中山大学中山医学院, 广东, 广州, 510080;
3. 白云区妇幼保健院儿科, 广东, 广州, 510400

出版日期:2005-03-20 发布日期:2005-03-20
基金资助:
收稿日期:2004-11-9。
作者简介:庞建新(1965- ),男,博士,副教授,电话:020-61648235,E-mail:pjx@fimmu.com

Total alkaloid of Macleaya cordata: in vitro cytotoxic effect on Hep3B cells and in vivo antitumor effect in mice

PANG Jian-xin¹, MA Ren-qiang², LIU Lan-mei³, JIANG Yi-ping¹, SUN Li-sha¹

1. 南方医科大学药理教研室, 广东, 广州, 510515;
2. 中山大学中山医学院, 广东, 广州, 510080;
3. 白云区妇幼保健院儿科, 广东, 广州, 510400

Online:2005-03-20 Published:2005-03-20

摘要/Abstract

摘要： 目的观察博落回总碱(TAPP)的体内外抗肿瘤活性作用。方法 MTT法检测TAPP体外对人肝癌Hep3B细胞、小鼠H22肝癌细胞的抑瘤作用;用小鼠移植性肿瘤法检测TAPP对小鼠H22肝癌细胞、S180肿瘤细胞的体内抑瘤作用。测3次重复实验结果。结果 (1)TAPP在体外有明显的细胞毒性作用,可抑制Hep3B、H22细胞增殖,且呈剂量依赖性:其对Hep3B细胞的半数抑制浓度(IC₅₀) 3次重复实验结果分别为3.04、3.98、2.98µg/ml,对H22细胞则分别为2.89、2.21、2.34µg/ml。(2)体内实验表明,TAPP可抑制H22细胞皮下移植瘤的生长,在剂量为每天1、2、4 mg/kg·b.w.时,3次腹腔注射给药实验测得抑瘤率分别为18.6%、35.1%、44.9%,而以每天4 mg/kg·b.w.时口服给药抑瘤率则为7.9%;另外,TAPP可明显延长S180腹水瘤小鼠存活时间,剂量为每天1、2、4 mg/kg·b.w. 时静脉注射给药生命延长率3次重复结果平均分别为24.8%、48.9%、52.7%。结论 TAPP在体内外均有明显的抗肿瘤活性。

Abstract: Objective To observe the cytotoxic effects in vitro and antitumor effects in vivo of total alkaloid of Macleaya cordata.Methods MTT assay was used to assess the proliferation of Hep3B and H22 cells in vitro treated with the alkloid, and the inhibitory effects of the alkaloid on H22 and S180 tumors were observed in mice with subcutaneous inoculation of the tumor cells.Results The total alkaloid significantly inhibited the proliferation of human Hep3B cells and murine H22 cells in a dose-dependent in vitro. IC₅₀ of the alkloid in 3 repeated experiments was 3.04, 3.98 and 2.98µg/ml respectively in Hep3B cells, and was 2.89, 2.21 and 2.34µg/ml in H22 cells. In the tumor-bearing mice, the alkaloid inhibited the development of H22 tumor and prolonged the survival of S180 tumor-bearing mice. At the daily dose of 1, 2, and 4 mg/kg·b.w (i.p.) and 4 mg/kg·b.w. (i.g.) for 10 days, the inhibition rates of the alkaloid on H22 tumor in 3 repeated experiments were 18.6%, 35.1%, 44.9% and 7.9% respectively, and the rates of survival prolongation of the tumor-bearing mice were 24.8%, 48.9%, and 52.7%, respectively.Conclusion The alkloid possesses antitumor effects both in vitro and in vivo.

中图分类号:

R965

庞建新¹, 马仁强², 刘兰梅³, 蒋毅萍¹, 孙莉莎¹. 博落回总碱对肝癌细胞的毒性作用和体内抗肿瘤作用[J]. 南方医科大学学报, 2005, 25(03): 325-328.

PANG Jian-xin¹, MA Ren-qiang², LIU Lan-mei³, JIANG Yi-ping¹, SUN Li-sha¹. Total alkaloid of Macleaya cordata: in vitro cytotoxic effect on Hep3B cells and in vivo antitumor effect in mice[J]. Journal of Southern Medical University, 2005, 25(03): 325-328.

参考文献

[1] 杨军,王静,刘信顺,等.博落回的药效研究[J].中药材,1999,22(2):82-5.Yang J,Wang J. Experimental studies on pharmacodynamic effect of Macleaya. cordata[J]. J Chin Med Mat,1999,22(2):82-5.
[2] Chmura SJ,Dolan ME,Cha A,et al. In vitro and in vivo activity of protein kinase C inhibitor chelerythrine chloride induces tumor cell toxicity and growth delay in vivo [J]. Clin Cancer Res,2000,6(2):737-42.
[3] Hoffmann TK,Leenen K,Hafner D,et al. Antitumor activity of protein kinase C inhibitors and cisplatin in human head and neck squamous cell carcinoma lines [J]. Anticancer Drugs,2002,13(1):93-100.
[4] 袁涛忠,张华生.博落回杀灭蝇蛆效果的实验观察[J].寄生虫及寄生虫病学杂志,1999,21:128.
[5] 樊淑莲,焦峰,张园,等.博落回总生物碱对动物移植性肿瘤的作用研究[J].陕西肿瘤医学,2000,8(3):174-9.
[6] 吴茂旺,朱建华.博落回药理研究与应用概况[J].基层中药杂志2002,16(3):46-8.
[7] 任新玲,沈丽英,金伯泉,等.表皮生长因子受体单克隆抗体抗肺癌作用的研究[J].肿瘤,2000,20(1):35-7.Ren XL,Shen Ly,Jin BQ,et al. Efficacy of epidermal growth factor receptor antibody against lung cancer in vitro and in nude mice [J].Tumor,2000,20(1):35-7.
[8] 徐淑云,卞如濂,陈修.药理实验方法学[M].人民卫生出版社,1991.1428.
[9] 李仪奎.中药药理实验方法学[M].上海科学技术出版社,1991.513.
[10] 彭海鹏.博落回的开发利用[J].中国野生植物资源(Chin Wild Plant Resour),2003,22(3):58.
[11] Herbert JM,Augereau JM,Gleye J,et al. Chelerythrine is a potent and specific inhibitor of protein kinase C [J]. Biochem Biophys Res Commun,1990,172(3):993-9.
[12] Olivero P,Stutzin A. Calcium modulates osmosensitive taurine efflux in HeLa cells[J]. Neurochem Res,2004,29(1):169-76.
[13] Kim J,Lin J,Adam RM,et al. An oxidative stress mechanism mediates chelerythrine-induced heparin-binding EGF-like growth factor ectodomain shedding [J]. J Cell B iochem,2004,15 [Epub ahead of print].
[14] Faddeeva MD,Beliaeva TN. Sanguinarine and ellipticine cytotoxic alkaloids isolated from well-known antitumor plants. Intracellular targets of their action [J]. Tsitologiia,1997,39(2-3):181-208.