福安泰-03对小鼠癌细胞转移相关基因和转移行为的影响

Effects of Intraperitoneal Injection of Fuantai-03 on Metastasis-related Genes and Metastasis in Mouse Lewis Lung Carcinoma and B16 Melanoma

以小鼠Lewis肺癌(Lewis lung carcinoma,LLC)自发转移和小鼠黑色素瘤(B16)细胞实验转移为模型,检测福安泰-03(Fuantai-03,FAT-03)对小鼠Lewis肺癌生长和转移的影响,Western印迹和免疫组化法分析FAT-03对小鼠Lewis肺癌转移相关基因CD44和nm23-H1表达水平的影响。结果显示,FAT-03明显抑制LLC的生长和肝转移,显著抑制B16细胞的肺转移,并与环磷酰胺(CY)有协同作用。每天腹腔注射FAT-03 10.0、20.0 mg/kg,共用药14天,对LLC生长的抑制率分别为53.8%、61.3%(CY的抑制率为58.8%);对LLC肝转移的抑制率分别为37.4%、76.5%(CY的抑制率为64.5%)。对B16细胞肺转移的抑制率分别为51.4%和63.7%(CY的抑制率为44.0%,10.0mg/kg FAT-03+CY的抑制率为88.1%)。显著下调促癌转移基因CD44,上调抑癌转移基因nm23-H1的表达。结果提示FAT-03值得作为一种具有抗癌转移作用的先导物质继续研究,它的抗癌转移效果可能部分与其下调促癌转移基因CD44和上调抑癌转移基因nm23-H1的表达有关。

Western blot analysis and immunohistochemistry protocol were performed to assay the expressions of CD44 and nm23-H1; mouse Lewis lung carcinoma （LLC）, a spontaneous tumor metastasis model, and mouse B 16 melanoma （B 16）, a experimental tumor metastasis model, were utilized to study the effects of intraperitoneal （ip） injection of Fuantai-03 （FAT-03） on cancer metastasis. The results showed that FAT-03 resulted in downregulation of expression of CD44, and up-regulation of expression of nm23-H1 in vitro and in vivo, and that the growth inhibition rates of primary tumors of LLC in the FAT-03 [10.0, 20.0 mg/（kg·d）, ip, for 14 days]-administered mice were 53.8% and 61.3% [vs 58.8% of cyclophosphamide （CY） ], and the liver metastasis inhibition rates （MIR） of LLC were 37.4% and 76.5% （vs. 64.5% of CY）, and the lung MIR of B16 were 51.4% and 63.7% （vs 44.0% of CY, and 88.1% of 10.0 mg/kg FAT-03＋CY）, respectively. These observations qualify FAT-03 as an interesting lead component to prevent cancer metastasis; FAT-03-induced change of expressions of metastasis-related genes may be partially responsble for its inhibitory effect on metastasis.