黄蘑碱溶性多糖对荷瘤小鼠MMPs表达的调节及其抗肿瘤作用机制

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目的:观察黄蘑碱溶性多糖(Fb)对荷瘤小鼠基质金属蛋白酶(MMPs)的调节作用,探讨其抗肝癌作用机理。方法:建立小鼠体内移植性肝癌模型,随机分为5组:阴性对照组(control),阳性对照环磷酰胺组(CTX)和Fb小、中、大剂量治疗组(Fb20,Fb40和Fb80)。测定Fb抑瘤率(IR),观察其整体抗肝癌作用;用明胶酶谱分析和电泳凝胶定量分析系统测定酶解条带的灰度值观察肿瘤组织MMP-2和MMP-9表达水平;免疫组化方法检测种植性肝癌组织内MMPs及其组织抑制因子(TIMPs)的阳性率和分布特点,分析Fb对其蛋白表达的调节作用。结果:Fb20、Fb40和Fb803个治疗组肝癌H22抑瘤率分别为38.7%、51.2%和58.3%,与阴性对照组比较明显增高(P<0.05或P<0.01);Fb40和Fb80组肿瘤组织内TIMP-1表达率分别高达70.0%和84.5%,与阴性对照组(41.7%)和CTX组(44.4%)比较均表现出明显的上调作用(P<0.05);Fb40和Fb80组肿瘤组织内MMP-9的表达分别为47.7%和44.4%,与阴性对照组(60.0%)比较,显示Fb对肝癌组织中MMP-9有下调趋势,但无统计学意义(P>0.05);Fb40组MMP-2表达阳性率为20.0%,与阴性对照(58.3%)比较有明显下调作用(P<0.05)。结论:Fb可以有效地抑制移植性肝癌H22在小鼠体内的生长和侵袭,其作用机制可能与其对MMPs/TIMPs活性的调节有关。 OBJECTIVE: To observe the regulation of matrix metalloproteinases (MMPs) in the tumor-bearing mice by the alkali-soluble polysaccharide (Fb) from Huangmuzi and to explore its anti-hepatocarcinogenic mechanism. METHODS: A mouse model of transplanted liver cancer was established and randomly divided into 5 groups: negative control (control), positive control cyclophosphamide (CTX) and Fb small, medium and high dose treatment groups (Fb20, Fb40 and Fb80). . The inhibition rate of Fb (IR) was measured, and the anti-hepatocarcinoma effect was observed. The expression of MMP-2 and MMP-9 in the tumor tissue was observed by gelatin zymography and electrophoresis gel quantitative analysis system. Immunohistochemical method was used to detect the positive rate and distribution characteristics of MMPs and tissue inhibitory molecules (TIMPs) in the tissue of implanted hepatocellular carcinoma, and analyze the regulation effect of Fb on its protein expression. RESULTS: The tumor inhibition rates of H22 tumors in Fb20, Fb40, and Fb803 treatment groups were 38.7%, 51.2%, and 58.3%, respectively, which were significantly higher than those in the negative control group (P<0.05 or P<0.01); tumor tissues in the Fb40 and Fb80 groups were within The expression rates of TIMP-1 were as high as 70.0% and 84.5%, respectively. Compared with the negative control group (41.7%) and the CTX group (44.4%), they showed significant up-regulation (P<0.05); MMPs in the tumor tissues of the Fb40 and Fb80 groups. The expression of -9 was 47.7% and 44.4%, respectively. Compared with the negative control group (60.0%), Fb showed a trend of down-regulation of MMP-9 in HCC tissues, but it was not statistically significant (P>0.05). Fb40 MMP- 2 The positive rate of expression was 20.0%, which was significantly down-regulated compared with the negative control (58.3%) (P<0.05). Conclusion: Fb can effectively inhibit the growth and invasion of transplanted hepatocellular carcinoma H22 in mice. Its mechanism may be related to its regulation of MMPs/TIMPs activity.
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