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目的探讨蝎毒多肽增强5-氟尿嘧啶(5-Fu)对肝癌H22抑制作用的机制。方法以接种H22肝癌小鼠腹水方法建立小鼠荷瘤模型,在接种后第7天将荷瘤小鼠随机分为模型组、蝎毒多肽(20 mg/kg)组、5-Fu(15 mg/kg)组、低剂量蝎毒多肽(5 mg/kg)+5-Fu组、高剂量蝎毒多肽(20 mg/kg)+5-Fu组,每组10只,连续给药21 d。绘制肿瘤体积增长曲线并计算抑瘤率;CD34标记肿瘤微血管;免疫组织化学法检测核因子-κB(NF-κB)、基质金属蛋白酶-9(MMP-9)和血管内皮生长因子(VEGF)蛋白表达。结果与模型组相比,联合给药组H22肝癌移植瘤的生长受到明显抑制(P<0.01),微血管密度(MVD)及NF-κB、MMP-9、VEGF蛋白表达均明显降低(P<0.01);与5-Fu组相比,高剂量蝎毒多肽+5-Fu组的MVD及NF-κB、MMP-9、VEGF蛋白表达也显著降低(P<0.01),而低剂量蝎毒多肽+5-Fu组则无显著改变。结论蝎毒多肽可增加5-Fu对肿瘤组织的抑制作用,其机制可能与抑制H22肝癌组织NF-κB通路及MMP-9、VEGF的表达,从而抑制新生血管形成有关。
Objective To explore the mechanism of scorpion venom peptide (5-Fu) on H22 inhibition of liver cancer. Methods The tumor-bearing mice model was established by inoculation of ascites of H22 hepatocarcinoma mice. The tumor-bearing mice were randomly divided into model group, scorpion venom peptide (20 mg / kg) group, 5-Fu low dose of scorpion venom peptide (5 mg / kg) + 5-Fu group and high dose of scorpion venom peptide (20 mg / kg) + 5-Fu group were administrated for 10 days. The tumor volume growth curve was plotted and the tumor inhibition rate was calculated. CD34 was used to mark tumor microvessels. The expressions of nuclear factor-κB, MMP-9 and VEGF were detected by immunohistochemistry expression. Results Compared with the model group, the growth of H22 hepatocellular carcinoma in combination group was significantly inhibited (P <0.01), while the microvessel density (MVD) and the expression of NF-κB, MMP-9 and VEGF were significantly decreased ). Compared with 5-Fu group, the expression of MVD and NF-κB, MMP-9 and VEGF in high-dose scorpion venom peptide + 5-Fu group were also significantly decreased 5-Fu group did not change significantly. Conclusions Scorpion venom polypeptide can increase the inhibitory effect of 5-Fu on tumor tissue, and its mechanism may be related to the inhibition of the expression of NF-κB pathway and MMP-9 and VEGF in H22 hepatocellular carcinoma and thus the inhibition of neovascularization.