紫杉醇节律化疗联合EGCG抑制胃癌生长和肿瘤血管生成的实验研究

Metronomic paclitaxel combined with EGCG inhibits growth of gastric cancer and angiogenesis

目的:探讨低剂量紫杉醇联合表没食子儿茶素没食子酸酯(EGCG)对胃癌肿瘤血管生成的影响,并观察其抑瘤效果。方法:建立裸鼠人胃癌移植瘤模型,分别给予0.9%NaCl溶液、最大耐受剂量(MTD)紫杉醇、低剂量紫杉醇、EGCG及低剂量紫杉醇联合EGCG腹腔注射,观察肿瘤生长情况。免疫组化染色,测定CD31和血管内皮生长因子(VEGF)表达情况。结果:对照组肿瘤生长迅速,其他治疗组肿瘤生长都受到了抑制,联合治疗组抑瘤效果最明显,各组比较差异有统计学意义,P<0.05。与对照组及MTD组相比,低剂量紫杉醇组肿瘤组织内的微血管密度(MVD)及VEGF表达均下降,合用EGCG后,MVD和VEGF表达下降更明显,P<0.05。结论:低剂量紫杉醇化疗能够有效抑制裸鼠胃癌移植瘤的生长及微血管的形成,与EGCG联合应用时效果增强。

OBJECTIVE： To evaluate the anti-angiogenic and anti-tumor effects of low dose paclitaxel combined with （-） epigallocatechin-a-gallate （EGCG） on gastric cancer. METHODS： Nude mice bearing BGC-823 human gastric carcinoma were randomized into five groups. The nude mice were administered by sterile saline（0.9%）, maximum tolerable dose （MTD） paclitaxel, low-dose paclitaxel, EGCG and low dose paclitaxel combined with EGCG, respectively. Tumor growth was monitored in each group. Expression of microvessel density （MVD） and VEGF was detected by imunohisto- chemical staining. RESULTS： The gastric cancer xenografts grew rapidly in the control group. The tumor growth was inhibited in other treatment groups and the inhibitory ratio was highest in low-dose paclitaxel plus EGCG trealment group （P〈0.05）. Compared with saline control and MTD paclitaxel groups, MVD and expression of VEGF were decreased in low-dose paclitaxel group. When low dose paclitaxel and EGCG were used in combination, the MVD and the ex pression of VEGF decreased more significantly （ P〈 0.05 ）. CONCLUSION： Low dose paclitaxel can inhibit the growth of gastric tumour and the formation of microvessels and the effects were im proved by concurrent administration of EGCG.