白鹤方对人胃癌裸小鼠原位移植瘤微血管密度、MMP-9表达的影响

目的观察白鹤方对人胃癌BGC-823裸鼠原位移植瘤生长和转移的抑制作用,以及对移植瘤组织微血管密度(MVD)、基质金属蛋白酶-9(MMP-9)表达的影响。方法 60只裸鼠建立人胃癌BGC-823原位移植瘤模型,随机分为白鹤方组、5-氟尿嘧啶(5-FU)组、白鹤方与5-FU联合治疗组和模型组,每组15只。白鹤方组给予白鹤方(0.2 g/ml) 0.5 ml灌胃,1次/d; 5-FU组予5-FU稀释液(6 mg/ml) 0.2 ml腹腔注射,1次/周;白鹤方与5-FU联合治疗组,予白鹤方(0.2 g/ml) 0.5 ml灌胃,1次/d,同时予5-FU稀释液(6 mg/ml) 0.2 ml腹腔注射,1次/周。模型组予0.9%NaCl溶液0.5 ml/d灌胃,1次/d。用药6周后结束实验,观察各组裸鼠原位移植瘤生长和转移情况,测瘤体质量,计算抑瘤率;电镜下观察移植瘤超微结构;免疫组化检测各组裸鼠移植瘤组织MVD和MMP-9表达情况。结果白鹤方组、5-FU组、白鹤方与5-FU联合治疗组移植瘤体质量明显低于模型组,抑瘤率分别为48.65%、47.64%和54.39%;电镜下观察发现,白鹤方组、5-FU组、白鹤方与5-FU联合治疗组胃癌细胞均出现凋亡表现;白鹤方组、白鹤方与5-FU联合治疗组移植瘤组织MVD和MMP-9表达低于5-FU组和模型组(P0.05)。结论白鹤方对人胃癌BGC-823裸鼠原位移植瘤生长和转移具有抑制作用,能降低移植瘤组织MVD,抑制微血管生成;可能是通过下调MMP-9表达而发挥作用。

Effects of Baihe Recipe on microvascular density and MMP-9 expression in nude mice orthotopically transplanted with human gastric carcinoma

  Objective:To investigate the inhibitory effect of Baihe Recipe on growth and metastasis of orthotopically transplanted human gastric carcinoma BGC-823 in nude mice and the effects on microvascular density (MVD) and the expression of matrix metalloproteinases-9 (MMP-9) in the tumor tissues. MethodsSixty nude mice orthotopically transplanted with human gastric cancer BGC-823 cells were randomly assigned into four groups:Baihe recipe group, 5-fluorourcil (5-FU) group, Baihe recipe + 5-FU group and model group, 15 mice in each group. The Baihe recipe group received Baihe recipe 0.5 ml (0.2 g/ml) by gastric gavage once a day, the 5-FU group was intraperitoneally administered 5-Fu dilution 0.2 ml (6 mg/ml) once a week, the Baihe recipe + 5-FU group was administered Baihe recipe 0.5 ml (0.2 g/ml) by gastric gavage once a day and 5-FU dilution 0.2 ml (6 mg/ml) intraperitoneally once a week, and the untreated group was given 0.9% NaCl solution 0.5 ml by gastric gavege once a day. When the experiment was completed at 6 weeks after administration, the growth and metastasis of the orthotopically transplanted tumor in nude mice was observed and tumor mass was measured to calculate the tumor inhibition rate in each group. The ultrastructure was observed under electron microscopy. MVD and the expression of MMP-9 were detected in the tumor tissues by immunohistochemistry in each group.  Results:The tumor mass was obviously lower in the Baihe recipe, the 5-FU and the Baihe recipe + 5-FU groups than in the model group, with an inhibition rate of 48.65%, 47.64% and 54.39% respectively. Under electron microscope, the gastric cancer cells showed apoptosis in the Baihe recipe, the 5-FU and the Baihe recipe + 5-FU groups. MVD and the expression of MMP-9 in the tumor tissues decreased in the Baihe recipe and the Baihe recipe + 5-FU groups compared to the 5-FU and the model groups (P<0.05).  Conclusion:Baihe recipe inhibits the growth and metastasis of human gastric cancer BGC-823 orthotopically transplanted in nude mice, reduces MVD and inhibits microangiogenesis in the tumor tissues, probably by down-regulating the expression of MMP-9.