益气活血解毒方对小鼠Lewis肺癌移植瘤自发性肺转移的作用及机制探讨

目的研究益气活血解毒方(由人参皂苷、三七皂苷、小檗碱组成)对小鼠Lewis肺癌自发性肺转移的作用并探讨其作用机制。方法复制小鼠Lewis肺癌模型,腹腔注射给药20 d后观察肺表面转移瘤结节数;常规石蜡切片HE染色,观察肺内转移灶的数量和大小;免疫组化法检测瘤细胞及瘤组织中E-钙黏附素、CD44、基质金属蛋白酶-2(MMP-2)、金属蛋白酶组织抑制因子-2(TIMP-2)的表达。结果益气活血解毒方能减少肺转移灶数,给药组转移灶的面积明显小于对照组;并能促进肿瘤细胞E-钙黏附素的表达而抑制CD44的表达,降低肿瘤组织MMP-2/TIMP-2的比值。结论益气活血解毒方能抑制小鼠Lewis肺癌的自发性肺转移;其机制可能是调节肿瘤细胞黏附分子表达,避免瘤细胞从原发灶的脱落,并抑制肿瘤细胞与基质和内皮细胞的黏附,以及抑制细胞外基质的降解,从而阻止肿瘤细胞的侵袭转移。

Effect of Yiqihuoxuejiedu Formula on spontaneous metastasis of mouse Lewis lung carcinoma and its mechanism

Objective To study the effect of Yiqihuoxuejiedu Formula composed of panaxoside,(arasaponin) and berberin on the spontaneous metastasis of mouse Lewis lung carcinoma and to discuss the mechanism.Methods The mouse model of Lewis lung carcinoma was established and then the mice were given Yiqihuoxuejiedu Formula by intraperitoneal injection.After 20 days the number of metastatic nodes on lung surface was counted,the number and size of metastatic focus in lung Paraffin section stained by HE were observed.Immunohistochemistry was used to detecte the expressions of E-cadherin,CD44,matrix metalloproteinase-2(MMP-2) and tissue inhibitor of metalloproteinase-2(TIMP-2) in tumor cells or tissue.Results Yiqihuoxuejiedu Formula decreased the number and size of metastatic focus.The size of metastatic focus was significantly smaller in Yiqihuoxuejiedu Formula group than that in the control group.Furthermore Yiqihuoxuejiedu Formula increased E-cadherin expression,and inhibited CD44(expression,)and decreased the ratio of MMP-2 to TIMP-2 in the tumor tissue.Conclusion Yiqihuoxuejiedu Formula can inhibit the spontaneous metastasis of Lewis lung carcinoma in mice.The mechanism may be related to that Yiqihuoxuejiedu Formula can prevent the exuviation of tumor cells from primary carcinoma,inhibit the adhesion of tumor cells to extracellular matrix(ECM) and endothelial cells,and degradation of ECM by regulating the expression of cell adhesion molecules in tumor cells,and to prohibit the invasion and metastasis of tumor cells.