土贝母苷甲对小鼠B16 黑色素瘤和Lewis 肺癌转移的抑制作用

中国临床药理学与治疗学 ›› 2006, Vol. 11 ›› Issue (7): 764-770.

土贝母苷甲对小鼠B16 黑色素瘤和Lewis 肺癌转移的抑制作用

王长秀, 马润娣, 于立坚

广东海洋大学广东省海洋药物研究与开发重点实验室, 湛江 524025, 广东

收稿日期:2006-02-21 修回日期:2006-04-03 出版日期:2006-07-26 发布日期:2020-10-30
通讯作者: 马润娣,女, 博士生导师, 研究员, 研究方向:肿瘤药物作用的靶点。Tel:0759-2362480 E-mail:ywyj9578@sohu.com
作者简介:王长秀, 女, 硕士研究生, 研究方向:天然药物。Tel:0759-2388634 E-mail:wxiaomin412@163.com

Inhibitory effects of tubeimoside 1, a cyclic bisdesmoside isolated from Bolbostemma paniculatum, on metastases of mouse B16 melanoma and lewis lung carcinoma

WANG Chang-xiu, MA Run-di, YU Li-jian

Guangdong Provincial Key Laboratory of Marine Materia Medica, Guangdong Ocean University , Zhanjiang 524025,Guangdong, China

Received:2006-02-21 Revised:2006-04-03 Online:2006-07-26 Published:2020-10-30

摘要/Abstract

摘要： 目的本研究旨在探讨土贝母苷甲对小鼠B16 黑色素瘤和Lewis 肺癌转移的影响。方法采用裸BALB/c 小鼠B16 黑色素瘤实验转移和裸BALB/c小鼠Lewis 肺癌自发转移模型研究土贝母苷甲对肿瘤转移的影响;采用免疫组织化学法检测土贝母苷甲对转移相关基因CD44v 6 、ErbB-2 和nm23-H1 表达的影响。结果腹腔注射低于全身中毒水平剂量的土贝母苷甲明显减少接种B16 黑色素瘤细胞小鼠的肺重和肺转移灶数量, 而对小鼠的健康和活力无明显影响;土贝母苷甲(2 、3 mg·kg^-1·d^-1 ×14 d) 和环磷酰胺(50 mg·kg^-1 ·wk^-1 ×2 d) 对B16 黑色素瘤细胞肺转移的抑制率分别为68.8 %、82.8 %和49.1 %。土贝母苷甲治疗组小鼠Lewis 肺癌原发肿瘤的平均瘤重明显低于对照组(P<0.05) 。土贝母苷甲(2 、3 mg·kg^-1·d^-1 × 14 d ) 和环磷酰胺(50 mg·kg^-1·w^-1 ×2 d) 治疗组小鼠的肝转移抑制率分别为46.3 %、52.0 %和54.7 %。土贝母苷甲显著下调促转移基因CD44v6 和ErbB-2 的表达, 上调抑转移基因nm23-H1 的表达。结论土贝母苷甲对小鼠B16 黑色素瘤的实验性转移和Lewis 肺癌的自发性转移都有显著的抑制作用。土贝母苷甲对肿瘤转移的这种抑制作用与其抑制原发肿瘤生长、下调促转移基因CD44v6 和ErbB-2 及上调抑转移基因nm23-H1 的表达有关, 提示土贝母苷甲是一个阻止癌扩散和转移的候补化合物。

关键词: 土贝母, 土贝母苷甲, 癌转移, B16 黑色素瘤, Lewis 肺癌, 转移相关基因

Abstract: AIM: To investigate the effects of tubeimoside 1 on the metastases of mouse B16 melanoma and lewis lung carcinoma.METHODS: The effects of tubeimoside 1 on metastasis were studied by using an experimental metastasis model of mouse B16 melanoma cell line and a spontaneous metastasis model of mouse lewis lung carcinoma.The effects of tubeimoside 1 on the expressions of CD44v6, ErbB-2, and nm23-H1 were studied by using streptavidin-peroxidase two step immunohistochemical method.RESULTS: In mice that received i.v.injec-tion of mouse B16 melanoma cells, daily i.p.administration of tubeimoside 1-without reaching systemic toxicic levels-remakably reduced lung weight, and number of lung metastases, with preservation of apparently healthy and active behaviors.Lung metastasis inhibition rates of B16 melanoma cells by tubeimoside 1 (2, 3 mg·kg^-1·d^-1×14 d) and cyclophosphamide (50 mg·kg^-1 ·wk^-1 ×2d) were 68.8 %, 82.8 %, and 49.1 %, respectively.The weight of primary tumors of mouse lewis lung carcinomain the tubeimoside 1-administered mice was significantly less than that of the control (P<0.05).The liver metastasis inhibition rates of lewis lung carcinoma by tubeimoside1 (2, 3 mg·kg^-1·d^-1 ×14 d) and cyclophosphamide(50 mg·kg^-1 ·w^-1 × 2 d ) were 46.3 %,52.0 %, and 54.7, respectively.Treatment of tubeimoside1 apparently resulted in down-regulation of expressions of CD44v6 and ErbB-2, and up-regulation of expression of nm23-H1 in mouse lewis lung carcinoma cells.CONCLUSION: These observations qualify tubeimoside 1 as an interesting lead compound to prevent cancer spread and metastatic growth.

Key words: Bolbostemma paniculatum, tubeimoside1, cancer metastasis, mouse B16 melanoma, mouse lewis lung carcinoma, metastasis relnted gene

中图分类号:

王长秀, 马润娣, 于立坚. 土贝母苷甲对小鼠B16 黑色素瘤和Lewis 肺癌转移的抑制作用[J]. 中国临床药理学与治疗学, 2006, 11(7): 764-770.

WANG Chang-xiu, MA Run-di, YU Li-jian. Inhibitory effects of tubeimoside 1, a cyclic bisdesmoside isolated from Bolbostemma paniculatum, on metastases of mouse B16 melanoma and lewis lung carcinoma[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2006, 11(7): 764-770.

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