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CD44v6、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。
AIM: To investigate the effects of tubeimoside 1 on the metastases of mouse BI6 melanoma and lewis lung carcinoma. METHODS:The effects of tubeimoside 1 on metastasis were studied by using an experimental metastasis model of mouse BI6 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. REULTS: In mice that received i.v. injection of mouse B16 melanoma cells, daily i.p. administration of tubeimoside 1-without reaching systemic toxicic tevels-remakably reduced lung weight, and number of lung metastases, with preservation of apparently healthy and active behaviors. Lung metastasis inhibition rates of B 16 melanoma cells by tubeimoside 1 (2,3 mg·kg^-1·d^-1×14 d) and cyclophosphamide (50 mg·kg^-1·wk^-1×2 d) were 68.8%, 82.8%, and 49.1%, respectively. The weight of primary tumors of mouse lewis lung carcinoma in 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 tu-beimoside 1 (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 tubeimoside 1 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.
出处
《中国临床药理学与治疗学》
CAS
CSCD
2006年第7期764-770,共7页
Chinese Journal of Clinical Pharmacology and Therapeutics
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
Bolbostemma paniculatum
tubeimoside 1
cancer metastasis
mouse B16 melanoma
mouse lewis lung carcinoma
metastasis associate gene