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目的:探讨源于白眉蝮蛇的重组去整合素rAdinbitor对肝癌细胞H22生长的抑制作用及其机制。方法:通过诱导重组表达、纯化、鉴定等步骤获得rAdinbitor;采用右腋皮下注射1×106个H22细胞制备肝癌小鼠模型,随机分为模型组(0.9%氯化钠注射液0.2 ml/kg)、阳性对照组(重组人血管内皮抑制素1.65 mg/kg)和高、中、低剂量治疗组(rAdinbitor 5、1.25、0.5 mg/kg),每组8只,肌肉注射相应药物,每日1次,连续给药3周后处死小鼠,取瘤称质量,镜下观察肿瘤组织切片中5个视野下的血管数量。结果:成功诱导表达并纯化rAdinbitor,其蛋白含量为1.4 mg/ml,相对分子质量约为9 kD。各组小鼠瘤质量和血管数量分别为模型组:(1.513±0.922)g和3.34±0.58;阳性对照组:(0.562±0.304)g和1.33±0.58;高剂量治疗组:(0.318±0.205)g和1.18±0.56;中剂量治疗组:(0.434±0.323)g和1.32±0.60;低剂量治疗组:(0.536±0.328)g和1.35±0.58。与模型组比较,各剂量治疗组小鼠的瘤质量和血管数量均明显下降(P<0.05);与阳性对照组比较,中、高剂量治疗组小鼠的瘤质量差异有统计学意义(P<0.05),高剂量治疗组小鼠的血管数量差异有统计学意义(P<0.05),其余差异无统计学意义。结论:rAdinbitor对H22细胞的生长具有明显的抑制作用,其机制可能是抑制瘤组织周边新血管的形成。
OBJECTIVE: To investigate the inhibitory effect of rAdinbitor, a recombinant disintegrin, derived from Eimeria niloticus in the growth of H22 hepatocellular carcinoma cells and its mechanism. Methods: The rAdinbitor was obtained by induction of recombinant expression, purification and identification. The mouse model of HCC was established by subcutaneously injecting 1 × 106 H22 cells into the right axilla. The mice were randomly divided into model group (0.9% sodium chloride injection 0.2 ml / kg) , The positive control group (recombinant human endostatin 1.65 mg / kg) and the high, medium and low dose treatment group (rAdinbitor 5, 1.25, 0.5 mg / kg) The mice were sacrificed 3 weeks after continuous administration, and the tumors were weighed and the number of blood vessels in 5 fields under the microscope was observed microscopically. Results: The rAdinbitor was successfully induced and purified, with a protein content of 1.4 mg / ml and a relative molecular mass of about 9 kD. The tumor mass and blood vessel number in each group were respectively model group: (1.513 ± 0.922) g and 3.34 ± 0.58; positive control group (0.562 ± 0.304) g and 1.33 ± 0.58; high dose treatment group: (0.318 ± 0.205) g and 1.18 ± 0.56 respectively; the medium dose treatment group (0.434 ± 0.323) g and 1.32 ± 0.60; the low dose treatment group: (0.536 ± 0.328) g and 1.35 ± 0.58. Compared with the model group, the tumor mass and blood vessel number of mice in each dose treatment group were significantly decreased (P <0.05). Compared with the positive control group, the tumor mass in the medium and high dose treatment groups had statistically significant difference (P <0.05). There was significant difference in the numbers of blood vessels in the high-dose treatment group (P <0.05), while the other differences were not statistically significant. Conclusion: rAdinbitor has a significant inhibitory effect on the growth of H22 cells. The mechanism may be that it inhibits the formation of neovascularization around the tumor tissue.