地锦草水提液对H22荷瘤小鼠生长抑制及其机制探讨

目的：研究地锦草对H22荷瘤小鼠的抑瘤作用并探讨其对肿瘤组织血管内皮生长因子（vascular endothelial growth factor，VEGF）和基质金属蛋白酶-3（matrix metalloproteinases-3，MMP-3）蛋白表达的影响。方法：建立H22荷瘤小鼠模型，随机分为模型对照组、地锦草264mg／（kg·d）高剂量组、地锦草132mg／（kg·d）中剂量组、地锦草66mg／（kg·d）低剂量组和环磷酰胺组50mg／（kg·d）。灌胃给药14d后处死小鼠，剥离瘤组织，测量肿瘤体积大小。采用HE染色其形态学变化；免疫组化法观察肿瘤组织VEGF和MMP-3蛋白表达情况。结果：地锦草高剂量组的肿瘤体积为（3．125±1．711）mm2，模型对照组为（5．081±1．936）mm2；地锦草高剂量组肿瘤质量为（1．784±1．765）g，模型对照组为（4．418±2．720）g。与模型组比较，地锦草高剂量组肿瘤体积明显缩小，t=2．184，P=0．037；且其瘤质量减轻，t=2．145，P=0．041。地锦草和环磷酰胺组小鼠瘤体组织切片可见癌细胞聚积成巢，肿瘤细胞数量减少，多处组织坏死，瘤体与周围组织界限清楚，且未侵犯周围组织。免疫组化结果显示，模型组VEGF和MMP=3蛋白表达增强。地锦草高剂量组VEGF蛋白表达（0．160±0．004）下降，与模型对照组（0．228±0．020）比较差异有统计学意义，t=5．011，P〈0．001。地锦草高、中、低剂量组MMP=3蛋白表达分别为0．316±0．062、0．303±0．057和0．302±0．058，与模型组比较差异均有统计学意义，t值分别为6．322、6．845和6．534，P值均〈0．001。各组肿瘤组织的VEGF与MMP3蛋白表达无直接相关性，r=0．069，P=0．709。结论：地锦草可抑制H22荷瘤小鼠肿瘤的生长，其抗肿瘤机制可能与抑制H22荷瘤小鼠的肿瘤组织VEGF和MMP-3蛋白的表达有关。

Antitumor effect of Euphorbiae humifusae herb on H22 tumor-bearing mice and its mechanism

OBJECTIVE： To study the antitumor effects of euphorbiae humifusae herb （EHH） and the inferences on the expression of vascular endothelial growth factor （VEGF）,matrix metalloproteinases-3 （MMP-3）on H22 cells bearing mice. METHODS： H22 liver cancer cells were inoculated in the right axilla to prepare solid tumor models. Five groups were randomized in each batch, named model control group;a positive control group;a highdose group 264 mg/（kg · d）; a middle dose group 132 mg/（kg · d） and a low-dose group 66 mg/（kg · d）. The medication was given continuously for 14 days. The tumor was weighted and the tumor size was calculated. Histopathological morphology of the tumor were observed under optical microscope. Using immunohistochemical method, the protein expression of VEGF and MMP-3 in tumor tissues were determined. RESULTS： Compared with model control group, the size of tumor in EHH treat groups was smaller （3. 125±1. 711） mm3 vs （5. 081±1. 936） mma （t=2. 184,P=0. 037） and the weight of tumor was decreased （1. 784±1. 765） g vs （4. 418!2. 720） g（t=2. 145,P=0. 041）. Tumor cells was accumulated into a nest and the numberof cells decreased. Tissue necrosis was visible and normal tissue boundary was clear, not iniringe upon the surroundmg tissue. The immunohistochemical results showed that lower expression of VEGF in a high-dose groups （0. 160 ±0. 004） vs （0. 228±0. 020） ,t=5. 011 ,P〈0. 001 ,with comparison of the model control group. The expression of MMP-3 in different dose EHH （0. 316±0. 062,0. 303±0. 057 and 0. 302±0. 058） were decreased significantly comparing with those in model controls （t = 6. 322,6. 845 and 6.834, P〈0.001 ）. There wash＇ t a significant correlation between VEGF and MMP 3 （ r= 0. 069, P 〈 0. 709）. CONCLUSION： EHH acts on the inhibition of liver cancer cell and its mechanism is probably related to the decrease of the expressions of VEGF and MMP-3 in H22 tumor-bearing mice.