阿魏酸钠对小鼠H22肝癌生长的抑制作用及其机制研究

Inhibitory effect of Sodium Ferulate Injection on H22 cell growth of liver carcinoma in mouse model and its mechanism

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 Injection on H22 cell growth and angiogenesis of liver carcinoma, and the influence on the transcription of vascular endothelial growth factors （VEGF） mRNA in the mouse model. Methods The H22 cells of liver carcinoma were inoculated in KM mouse armpit hypodermically, Sodium Ferulate Injection was infected intrapertoneally, and then the tumor volume was measured every 3 days. The expressions of VEGF and proliferating cell nuclear antigen （ PCNA ） were detected by immunohistochemistry. The influence of Sodium Ferulate Injection on the proliferation of H22 cells and ECV 304 was tested by MTT method. The transcription of VEFG mRNA in tumor tissue was detected by RT-PCR. Results The volume and weight of H22 tumor grew more slowly in the Sodium Ferulate Injection group than in the control group （P 〈 0.05 ）. The capillary vessel density and VEGF and PCNA ceils in the tumor in the Sodium Ferulate Injection group were decreased significantly than those in the control group （ P 〈 0.05 ）. The transcription of VEGF mRNA in the Sodium Ferulate Injection group was decreased significantly than that in the control group （ P 〈 0.05 ）. The result of test in vitro showed that the Sodium Ferulate Injection group had no significant inhibitory effect on the proliferation of ECV304 and H22 ceils. Conclusion Sodium Ferulate Injection can inhibit significantly the H22 tumor growth, angiogenesis and the expression of VEGF, but not on the proliferation of ECV304 and H22 cells. The mechanism of anti-H22 tumor and anti-angiogenesis by Sodium Ferulate Injection may be related to that Sodium Ferulate Injection can inhibit VEGF expression in tumor tissue.