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目的:观察蜈蚣提取物(Scolopendra Centipede Extract,SCE)作用于裸鼠肝癌原位移植瘤模型后对肝癌原位移植瘤生长的抑制作用及EphA7蛋白的影响,探讨SCE抗肝癌的作用机制。方法:以肝内植入裸鼠肝癌组织法构建肝癌原位移植瘤模型。将成瘤裸鼠随机分为SCE高剂量组(蜈蚣提取物高剂量,50 mg/kg/d,腹腔注射)、SCE低剂量组(蜈蚣提取物低剂量,10mg/kg/d,腹腔注射)、5-FU组(50mg/kg/次,腹腔注射),模型组(0.9%氯化钠注射液,10g/kg/d,腹腔注射),另设正常组(同模型组),用药14d。观察裸鼠的瘤体体积与瘤重,计算抑瘤率,测血清AFP含量,检测移植瘤EphA7蛋白的表达情况。结果:(1)与模型组比较,SCE高剂量组、SCE低剂量组、5-FU组瘤重均低于模型组(P<0.01);与5-FU组及SCE低剂量组比较,SCE高剂量组平均瘤重最低,差异具有统计学意义(P<0.01);SCE高剂量组、SCE低剂量组、5-FU组抑瘤率分别是62.5%、37.5%、30.8%。(2)SCE高剂量组、SCE低剂量组血清AFP平均含量明显降低,与模型组比较,差异具有统计学意义(P<0.01);与5-FU组比较,SCE高剂量组血清中AFP含量明显降低(P<0.01),SCE低剂量组血清中AFP含量无明显差异(P>0.05)。(3)SCE高剂量组、SCE低剂组与模型组比较,肝癌原位移植瘤中Eph A7蛋白表达均表现为下调,差异具有统计学意义(P<0.01);与5-FU组比较,SCE高剂量组肝癌原位移植瘤中Eph A7蛋白表达下调,差异具有统计学意义(P<0.01),与SCE低剂量组比较,差异有统计学意义(P<0.01)。结论:SCE对肝癌原位移植瘤裸鼠肿瘤的生长有明显抑制作用,并有剂量依赖性;SCE通过下调Eph A7蛋白的表达,调控酪氨酸磷酸化及肿瘤血管的形成,可能是SCE抗肝癌的机制之一。
OBJECTIVE: To observe the effect of Scolopendra Centipede Extract (SCE) on the growth of orthotopic liver transplantation in situ in nude mice and the effect of scleopendra Centipede Extract on the expression of EphA7 protein. Methods: The orthotopic liver transplantation model of hepatocellular carcinoma was constructed by intrahepatic transplantation of hepatocellular carcinoma in nude mice. The tumor-bearing nude mice were randomly divided into SCE high dose group (centipede extract high dose, 50 mg / kg / d, intraperitoneal injection), SCE low dose group (centipede extract low dose, 10mg / kg / d, intraperitoneal injection) The model group (0.9% sodium chloride injection, 10g / kg / d, intraperitoneal injection) was used in the 5-FU group (50mg / kg / time, intraperitoneal injection). The tumor volume and tumor weight of the nude mice were observed. The tumor inhibition rate was calculated and the serum AFP level was measured. The expression of EphA7 protein was detected. Results: (1) Compared with model group, the tumor weight of SCE low dose group, SCE low dose group and 5-FU group were lower than that of model group (P <0.01); Compared with 5-FU group and SCE low dose group, SCE The average tumor weight in the high-dose group was the lowest (P <0.01). The inhibitory rates of high-dose SCE, low-dose SCE and 5-FU groups were 62.5%, 37.5% and 30.8%, respectively. (2) Compared with model group, the average level of serum AFP in SCE low dose group and SCE low dose group was significantly lower (P <0.01). Compared with 5-FU group, the serum AFP level in SCE high dose group (P <0.01). There was no significant difference in serum AFP levels in SCE low dose group (P> 0.05). (3) Compared with model group, SCE high dose group and SCE low dose group showed that Eph A7 protein expression was down-regulated in orthotopic liver transplantation tumor, the difference was statistically significant (P <0.01); Compared with 5-FU group, The level of Eph A7 protein in SCE high dose group was significantly lower than that in SCE low dose group (P <0.01). The difference was statistically significant (P <0.01). CONCLUSIONS: SCE significantly inhibits the growth of orthotopic transplanted hepatoma in nude mice in a dose-dependent manner. SCE regulates tyrosine phosphorylation and tumor angiogenesis by down-regulating the expression of Eph A7 protein One of the mechanisms of liver cancer.