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目的观察注射用阿魏酸钠对小鼠H22肝癌生长及血管生成抑制作用及其对血管内皮生长因子(VEGF)mRNA转录的影响。方法昆明小鼠前腋下皮下接种H22小鼠肝癌细胞,腹腔注射阿魏酸钠,每3 d测量1次肿瘤体积。用免疫组化法测定VEGF及增殖细胞核抗原(PCNA)的表达。MTT法检测阿魏酸钠对H22肿瘤细胞及血管内皮细胞(ECV304)增殖的影响,RT-PCR法测定肿瘤组织的VEGF mRNA的转录。结果阿魏酸钠组小鼠H22肿瘤体积、重量增长明显较对照组缓慢(P<0.05),同时阿魏酸钠组的肿瘤微血管密度及VEGF、PCNA阳性细胞较对照组显著减少(P<0.05)。阿魏酸钠组VEGF mRNA转录比对照组显著减少(P<0.05)。体外实验,阿魏酸钠对ECV304及H22细胞的增殖均无显著抑制作用。结论阿魏酸钠可以显著抑制小鼠H22肿瘤的生长及血管生成,且能抑制VEGF的表达,但不能抑制ECV304及H22细胞的增殖。阿魏酸钠对肿瘤组织VEGF表达的抑制作用可能是其抗H22肿瘤及抗血管生成的一个重要机制。
Objective To observe the inhibitory effect of sodium ferulate for injection on the growth and angiogenesis of mouse H22 hepatocarcinoma and its effect on the transcription of vascular endothelial growth factor (VEGF) mRNA. Methods Kunming mice were inoculated subcutaneously with H22 mouse hepatoma cells under the armpit before intraperitoneal injection of sodium ferulate. The tumor volume was measured every 3 days. Immunohistochemistry was used to detect the expression of VEGF and proliferating cell nuclear antigen (PCNA). The effect of sodium ferulate on the proliferation of H22 tumor cells and vascular endothelial cells (ECV304) was detected by MTT assay. The transcription of VEGF mRNA was detected by RT-PCR. Results The volume and weight gain of H22 tumor in sodium ferulate group were significantly slower than those in control group (P <0.05). At the same time, the microvessel density and VEGF, PCNA positive cells in sodium ferulate group were significantly decreased compared with those in control group (P <0.05 ). The expression of VEGF mRNA in the sodium ferulate group was significantly lower than that in the control group (P <0.05). In vitro experiments, sodium ferulate on ECV304 and H22 cell proliferation was no significant inhibitory effect. Conclusion Sodium ferulate can significantly inhibit the growth and angiogenesis of H22 tumor in mice, and can inhibit the expression of VEGF, but can not inhibit the proliferation of ECV304 and H22 cells. The inhibitory effect of sodium ferulate on VEGF expression in tumor tissue may be an important mechanism of anti-H22 tumor and anti-angiogenesis.