Objective: To investigate the dynamic changes in angiogenesis within the tumor tissue of mice bearing S180 tumor at different day-points of oral administration with a Chinese medicine compound "Yiliuyin" (YLY) and to explore the anti-tumor mechanisms of YLY in vivo.
Method: Fifty-six BALB/c mice were divided into YLY group and control group (28 mice/group) and each group was divided into four subgroups (7 mice/subgroup), randomly. After 24 hrs of inoculation with S180 tumor cells subcutaneously in the right axilla, YLY in the mice of YLY group and equal volume of cold boiled-water in the mice of control group were administered orally twice every day, 0.5 mL each time. The mice of one subgroup from the two groups apiece were killed at 10, 20, 30 th and 40 th day-point of oral administration, respectively. The tumors were isolated and were made into paraffin embedded sections. The dynamic changes of the angiogenesis (CD34 staining), vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor-2 (VEGFR-2) and endostatin (ES) in tumor tissue were detected by immunohistochemistry staining, and the results were shown as PED (positive enzyme dot).
Result: YLY could remarkably decrease the angiogenesis within tumor tissues. The PED of CD34 in control group at 10, 20, 30 th and 40 th day-point was 392.86+/-42.01, 481.49+/-58.34, 386.31+/-54.91 and 376.69+/-28.71, and that in YLY group was 334.46+/-33.38, 289.34+/-39.63, 257.09+/-40.00 and 246.57+/-36.78, respectively. The PED of CD34 in YLY group at each day-point was lower than that in control group (P<0.05, P<0.01, P<0.01 and P<0.01, respectively). The PED of VEGF in control group at 10, 20, 30 th and 40 th day-point was 852.63+/-81.65, 1168.40+/-96.69, 1292.60+/-147.54 and 1124.74+/-139.64, and that inYLY group was 718.40+/-94.94, 866.54+/-72.40, 859.31+/-74.02 and 753.34+/-72.95, respectively. The PED of VEGF in YLY group at each day-point was lower than that in control group (P <0.05, P <0.01, P <0.01 and P <0.01, respectively). The PED of VEGFR-2 in control group at 10th, 20th, 30th and 40th day-point was 618.63+/-59.08, 750.09+/-56.72, 684.91+/-72.86 and 644.06+/-60.25, and that in YLY group was 523.91+/-64.66, 449.03+/-46.85, 400.06+/-60.12 and 339.89+/-45.39, respectively. The PED of VEGFR-2 in YLY group at each day-point was lower than that in control group (P <0.05, P <0.01, P <0.01 and P <0.01, respectively). The PED of ES in control group at 10th, 20th, 30th and 40th day-point was 250.26+/-36.27, 298.60+/-44.41, 450.86+/-38.95 and 398.43+/-34.19, and that in YLY group was 249.57+/-40.23, 350.03+/-40.92, 499.40+/-40.29 and 497.94+/-42.76, respectively. There was no difference between the two groups at 10th day-point.The PED of ES in YLY group was higher than that in control group at 20, 30, 40 th day-point (P <0.05, P <0.01 and P <0.01, respectively) .
Conclusion: YLY could exert the anti- tumor role by down-regulating the expression of VEGF and VEGFR-2, up-regulating the expression of ES and inhibiting the angiogenesis within tumor tissue.