| Modern medicine has demonstrated that tumor metastasis is a complex and ordered biological process with Multiple steps, component elements and factors. With the development of cytobiology and molecular biology, several important points and molecular regulation in the process of metastasis were discovered. Based on theory of traditional Chinese medicine and results of empirical study, this research choose ginsenosides(GS), panax notoginside (PNS), berberine(Ber) to compose a formula called Yiqi-Huoxue-Jiedu(YHJ), which reflects principle of strengthening body resistance, activating blood circulation to dissipate blood stasis and heat-clearing and detoxicating. Utilizing varied modern techniques, this study investigated effect of YHJ on tumor growth and metastasis on level of organ, cell, molecule and gene and studied the effect of YHJ and its components on important points during metastasis and its molecular mechanisim so as to elucidate scientific principle of strengthening body resistance, activating blood circulation to dissipate blood stasis and heat-clearing and detoxicating and provide academic and experimental bases to advanced development and clinical application of anti-metastasis medications. Part I: Based on the model of murine Lewis lung carcinoma, the effect of YHJ(12mg·kg-1·d-1,with GS 5mg, PNS 5mg, Ber2mg;24mg·kg-1·d-1, with GS 10mg, PNS 10mg, Ber4mg)and Be(r2mg·kg-1·d-1,4mg·kg-1·d-1)on tumor growth and metastasis was investigated. Further study was made to research effect of YHJ on factors related with tumor metastasis in order to discuss its mechanism. 1.Murine Lewis lung carcinoma transplantation model was made and mice were administrated by intraperitoneal injection for 10 days. The results showed that YHJ and Ber could reduce tumor weight, index of tumor weight and expression of PCNA and the effect of YHJ was stronger than Ber. 2.The 21 day survival rate, the number of metastasis on lung surface and the area of metastasis in lung tissue were observed after 20 days administration .The results indicated that YHJ and Ber both increased survival rate of tumor-bearing mice and YHJ could reduce the number and area of metastasis. Ber also showed anti-metastasis effect, but its effect was inferior to YHJ. 3. Detected by immunohistochemical method and ELISA, the express of E-cadherin on tumor cells was increased and CD44 was decreased by YHJ. YHJ inhibited the expression of MMP-2 and promote the expression of TIMP-2, which resulted in descend of MMP-2/TIMP-2 ratio. Part II: Based on the model of high metastatic human giant cell lung carcinoma cell line and human umbilical vein endothelial cell (HUVEC), the effect of YHJ and its components on important points of metastasis and related molecules. 1.YHJ(240μg/ml, with GS100μg/ml,PNS100μg/ml,Ber40μg/ml;48μg/ml;24μg/ml) and its components could inhibit PG proliferation, but GS(50,100μg/ml) and PNS(50,100μg/ml) had weak effect and Ber(10,20,40μg/ml) had strong effect. Flow cytometry was used to detect the cell life cycle of PG and the result showed that YHJ and Ber could block PG in G0/G1 phase. More PG treated by YHJ and Ber presented apoptosis morphous and decline of mitochondrial membrane potential, witch demonstrates that it's possible that YHJ and Ber could induce apoptosis of tumor cells. 2. Detected by MTT, quantitative immunocytochemical method and RT-PCR, YHJ enhanced PG-PG homogeneous adhesion throμgh increasing the expression of E-cadherine protein and mRNA and weaken PG-matrix and PG-HUVEC adhesion throμgh decreasing the expression of CD44 protein and mRNA. The components of YHJ showed different effect. PNS had stronger effect of enhancing PG-PG adhesion and PG-matrix adhesion while Ber had stronger effect of enhancing PG-matrix and PG-HUVEC adhesion. 3. Agarose drop method was used to detect PG locomotivity and transwell cabin was used to detect PG chemotaxis locomotivity. The results demonstrated that YHJ prohibited PG locomotivity and chemotaxis locomotivity, while PNS showed promotion and GS...
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