药物研究
FENG Zhengquan;WU Liangcun;SHEN Minhe;SHU Qijin;WANG Binbin
2006, 25(12): 1249-1252.
To probe into the effects of the tailored shashen maidong decoction(TSMD) in the prevention and treatment of tumor metastases in mice and the underlying mechanisms. MethodsAliquots of the suspension containing tumor cells of the highly metastatic lung adenocarcinoma LA795 in mice were inoculated subcutaneously into T739 mice. 24 h after the challenge, mice bearing the tumor were randomly divided into 3 equal groups (n=20 in each group): the cyclophophamide(Cy) group, the TSMD group and the blank control group. Mice of the Cy group were given each an intraperitoneal injection of 60 mg·kg1 of Cy q.o.d. for 16 consecutive days. Mice of the TSMD group were given each 0.45 mL·d1 of TSMD q.d. administered by gastrogavage for 16 consecutive days. Mice of the blank control group were given each 0.45 mL·d1 of distalled water q.d. administered by gastrogavage for 16 consecutive days. The rate of tumor inhibition as reflected by the decrease in the weight of the subcutaneous tumor 20 days after the beginning of the drug treatment, the rate of inhibition of lung metastases, the survival span of the animals and expression of VEGF(vascular endothelial growth factor), CD34(vascular endothelial factor Ⅷ), CD44V6(adhesion molecule), MMT2(matrix metalloproteinase 2) and TIMP2(tissue inhibitor of metalloproteinase 2) by the subcutaneous tumors in mice of the different groups were compared. ResultsThe rate of tumor inhibition in mice treated with TSMD was 37.3%,which was , however , lower than that (57.3%)in mice treated with Cy(P＜0.01). The survival span of mice treated with TSMD was (31.4±2.5) days ,which was significantly longer than that (26.0±3.1 days) in mice of the blank control group but similar to that (30.1±3.6 days) in mice treated with Cy(P＞0.05). The expression of VEGF by the subcutanecous tumor in mice treated with TSMD was (2.6±1.4), which was significantly lower than that (5.2±3.2) in mice of the blank control group (P＜0.01) but similar to that (4.7±2.5 in mice treated with Cy(P＞0.05). The microvascular density (MVD) of the subcutaneous tumor in mice treated with TSMD was 10.2±1.7,which was strikinly lower than that (15.7±4.4) in mice of the blank control group (P＜0.01) but similar to that (10.2±1.7) in mice treated with Cy (P＞0.05). The expression of CD44V6 by the subcutaneous tumor in mice treated with TSMD was (2.1±1.9), which was significantly lower than that (4.1±2.6) in mice of the blank control group (P＜0.01) and than that (5.0±2.9) in mice treated with Cy (P＜0.01). The expression of TIMP2 by the subcutaneous tumor in mice treated with TSMD was (4.7±2.4), which was significantly higher than that (2.8±1.9) in mice of the blank control group(P＜0.01) but similar to that (3.6±1.5) in mice treated with Cy(P＞0.05) . The expression of MMP2 by the subcutaneous tumor in mice of the blank control group and those treated with TSMD and Cy were (4.8±3.6), (4.6±2.4) and (5.1±3.0), respectively, the differences between them being insignificant(P＞0.05, P＞0.05). A linear correlation was demonstrated between the number of lung metastases and VEGF,CD44V6 and MVD, the correlation coefficients being 0.490,0.398 and 0.455, respectively. Conclusion①TSMD was shown to inhibit tumor growth and lung metactaces, prolong survival span in mice bearing highly metastatic lung adenocarcinoma LA795. ② TSMD is thought by the authors to inhibit tumor metastases in a multipathway and multitarget manner by modulating adhesion, matrix degradation and expression of corresponding molecules relevant to angiogenesis during the process of tumor metatases.
