Han Zhipeng, Wang Runtian, Li Tiemin, Yang Zhiqiang, Cui Cheng, Ding Junying, Zhang Zhengzheng, Deng Yuqing, Wang Ping
Department of Immunology, Institute of Basic Medical Science, Hebei Medical University, Shijiazhuang 050017, China.
Zhongguo Zhong Yao Za Zhi. 2009 Jan;34(2):212-6.
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.
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).
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) .
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.
研究中药复方“抑瘤饮”(YLY)口服给药不同时间点对S180荷瘤小鼠肿瘤组织内血管生成的动态变化,探讨YLY体内抗肿瘤机制。
56只BALB/c小鼠随机分为YLY组和对照组(每组28只),每组再随机分为4个亚组(每组7只)。右腋皮下接种S180肿瘤细胞24小时后,YLY组小鼠每天口服YLY 2次,每次0.5 mL,对照组小鼠口服等体积冷开水。分别于给药第10、20、30和40天处死两组各1个亚组的小鼠,分离肿瘤并制成石蜡包埋切片。采用免疫组化染色检测肿瘤组织中血管生成(CD34染色)、血管内皮生长因子(VEGF)、血管内皮生长因子受体-2(VEGFR-2)和内皮抑素(ES)的动态变化,结果以阳性酶点数(PED)表示。
YLY可显著降低肿瘤组织内血管生成。对照组第10、20、30和40天CD34的PED分别为392.86±42.01、481.49±58.34、386.31±54.91和376.69±28.71,YLY组分别为334.46±33.38、289.34±39.63、257.09±40.00和246.57±36.78。YLY组各时间点CD34的PED均低于对照组(分别为P<0.05、P<0.01、P<0.01和P<0.01)。对照组第10、20、30和40天VEGF的PED分别为852.63±81.65、1168.40±96.69、1292.60±147.54和1124.74±139.64,YLY组分别为718.40±94.94、866.54±72.40、859.31±74.02和753.34±72.95。YLY组各时间点VEGF的PED均低于对照组(分别为P<0.05、P<0.01、P<0.01和P<0.01)。对照组第10、20、30和40天VEGFR-2的PED分别为618.63±59.08、750.09±