中药有效成分组方联合顺铂抑制小鼠肝癌血管生成的机制研究

Studies on the Anti-angiogenic Mechanism of the Formula of Chinese Medicine Active Ingredients Combined with Small Dose Cisplatin in Mice of Hepatocellular Carcinoma

摘要:

目的: 探讨中药有效成分组方(QHF:其中Q、H、F依次为"清热解毒"、"活血化瘀"、"扶正固本")联合小剂量化疗药物顺铂(DDP)抗小鼠H₂₂肝癌血管生成的作用机理。 方法: 48只BaLb/c小鼠右腋sc小鼠H₂₂肝癌细胞建立荷瘤模型,随机分设为QHF复方组、小剂量顺铂组(DDP)、联合用药组(QHF+DDP)及生理盐水组(NS)共4组。以抑瘤率为指标观察各药物对荷瘤小鼠肿瘤生长的抑制作用;免疫组化方法检测各药物对小鼠肝癌组织中的血管内皮生长因子(VEGF)、表皮生长因子受体(EGFR)及基质金属蛋白酶-2(MMP-2)表达的影响。 结果: QHF组、DDP组和联合用药组的瘤重均较NS对照组明显降低(P<0.01);联合用药组较QHF组明显降低(P<0.01),抑瘤率分别为47.45%,63.11%和72.95%。QHF组、DDP组和联合用药组小鼠移植瘤组织内VEGF,MMP-2的表达较NS对照组明显降低(P<0.05,P<0.01及P<0.01);小鼠移植瘤组织内EGFR的表达较NS对照组明显降低(P<0.01,P<0.05及P<0.01);联合用药组与各单药组之间的差异无统计学意义(P>0.05)。 结论: QHF复方与小剂量DDP均具有抗肝癌及抗肝癌血管生成的作用;QHF复方与小剂量DDP单独或联合应用抗血管生成作用的机制可能与其下调肝癌组织中VEGF,EGFR及MMP-2 的表达有关。

Abstract:

Objective: To investigate the anti-angiogenic mechanism of QHF (a formula of Chinese medicine ingredients, abbreviation Q for Qingrejiedu, H for Huoxuehuayu and F for Fuzhengguben) combined with small dose chemotherapy drug cisplatin(DDP)in H₂₂ mice of hepatocellular carcinoma. Method: The forty eight Balb/c mice were inoculated with cell suspension of mouse hepatocellular carcinoma cell line H₂₂ under the right axillary skin to establish the solid tumor model. Then they were randomly divided into four groups as follows: QHF group, DDP group, QHF+DDP group and NS (normal saline) group. The inhibition rates of tumor growth in tumor-bearing mice by drugs as an indicator were observed. The expression of VEGF, EGFR and MMP-2 in the tissue of mice tumor was detected with immunohistochemisty. Result: The weight of tumor was significantly lower in QHF, DDP and QHF+DDP group than that of in NS group(P<0.01), while the weight of mice tumor was significantly lower in QHF+DDP group than that of in QHF group. Their inhibition rate was 47.45%, 63.11%, 72.95%,respectively. The expression of VEGF and MMP-2 in the tissue of mice tumor was significantly lower in QHF, DDP and QHF+DDP group than that of in NS group(P<0.05, P<0.01 and P<0.01). Moreover, The expression of EGFR in the tissue of mice tumor was significantly lower in QHF, DDP and QHF+DDP group than that of in NS group(P<0.01, P<0.05 and P<0.01). However, the difference between QHF+DDP group and other groups has no significance(P>0.05). Conclusion: Both of QHF and small dose DDP have the anti-tumor and anti-angiogenic effect in H₂₂ mice of hepatocellular carcinoma. Moreover, one of anti-angiogenic mechanism may be concerned with the downregulation of the expression of VEGF, EGFR and MMP-2 in the tissue of mice tumor.