大黄素对结肠癌模型鼠两种细胞因子影响

Influence of Emodin on VEGF-C and MMP-9 of Mice with Colon Cancer

目的探讨大黄素对结肠癌裸鼠移植瘤模型的抗癌作用及其对血管内皮生长因子C(VEGF-C)和基质金属蛋白酶9(MMP-9)的影响。方法建立结肠癌裸鼠移植瘤模型,随机分成模型组,大黄素低、中、高剂量组和阳性对照组,每组10只。大黄素各剂量组分别给予大黄素50,100,150 mg·kg-1腹腔注射;阳性对照组给予氟尿嘧啶20.0 mg·kg-1腹腔注射,模型组给予等量0.9%氯化钠溶液。观察抑瘤率,TUNEL法检测凋亡指数,免疫组化法检测MMP-9和VEGF-C表达情况。结果与模型组比较,大黄素各剂量组结肠癌裸鼠移植瘤瘤体积、瘤质量、肿瘤抑制率和凋亡指数明显降低,差异有统计学意义(P<0.05或P<0.01);VEGF-C和MMP-9表达均不同程度降低。VEGF-C阳性表达大黄素中、高剂量组(0.68±0.36),(0.22±0.41)低于模型组(2.11±0.45),差异有统计学意义(P<0.05,P<0.01);MMP-9阳性表达(1.11±0.41),(0.38±0.44)低于模型组(2.31±0.39),差异有统计学意义(P<0.05,P<0.01)。结论大黄素具有较好的抑瘤效果,可能与诱导细胞凋亡和抑制VEGF-C、MMP-9表达有关。

Objective To explore antitumor effect of emodin on nude mice with human colon cancer xenografts, and VEGF-C and MMP-9 expression. Methods The human colon cancer xenografts model in nude mice were established and the mice were randomly divided into 5 groups with 10 mice in each. The emodin group were injected daily with emodin at doses of 50, 100 and 150 mg·kg^-1 , and the positive control group was injected daily with 5-Fu at the dose of 20 mg·kg^-1 while the positive control group was injected daily with normal saline. The tumor inhibition rate was observed and apoptosis index was detected by TUNEL, the expression of matrix metalloproteinase （MMP）-9 and vascular endothelial growth factor （VEGF）-C were investigated by immunohistochemical analysis. Results Compared with the model group, the tumor volume, tumor mass, tumor inhibition rate and apoptosis index of each dose group were significantly decreased（ P〈0.05, P〈0.01 ）, and the expression of VEGF-C and MMP-9 was lowered at various degree. VEGF-C expression in the medium and high dose of emodin group was significantly weaker（0.68±0.36）, （0.22±0.41） than that in the model group （2.11 ±0.45 ） （ P〈0.05, P〈0.01 ） and MMP-9 expression（ 1.11±0.41 ）, （0.38±0.44） was significantly lower than that in the model group（2.31±0.39） （P〈0.05, P〈0.01 ）. Conclusion Emodin effectively inhibits tumor growth, the mechanism of which may be related to the induction of apoptosis and inhibition of VEGF-C and MMP-9 expression.