蝮蛇毒抗高凝状态酶对小鼠肝癌抑制作用及P53、C-myc表达的影响

目的：建立实验性小鼠肝癌原位移植模型，在此基础上研究蝮蛇毒抗高凝状态酶（AHCSE）的抑癌作用并探讨其可能的作用机制。方法：将小鼠肝癌H22细胞种植于小鼠腋窝皮下，传代后取癌组织块种植于小鼠肝脏，进行不同剂量蛇毒制剂治疗的探索。将荷肝癌H22小鼠分成4组：模型对照组、AHCSE低、中、高剂量组（0．5、1．0、2．0mg／kg），给药10d后，根据瘤重计算抑瘤率，用免疫组化SP法计算P53、C—MYC阳性细胞数。结果：0．5、1．0、2．0mg／kg AHCSE的肿瘤抑制率分别为35．57％、50．38％、53．89％，P=53阳性细胞数为64、51、45，Cmyc阳性细胞数为46、38、34。1．0、2．0mg／kg AHCSE对小鼠移植性肝癌H22有较明显的抑制作用。结论：AHCSE对小鼠原位移植肝癌H22的生长具有一定的抑制作用，其机制可能与抑制突变型P53、CMYC蛋白的表达有关。

Effect of anti-hypercoagulability state enzyme of agkistrodon venom on hepatocarcinoma and expresion of P53,C-myc in mice

AIM:To research the inhibitory effect of antihypercoagulability state enzyme(AHCSE) of agkistrodon venom on the hepatocarcinoma in Balb/c mice bearing hepatocarcinoma (H22) strain in situ and its possible mechanisms. METHODS: Hepatic cancer H22 model in mice was established on axillary fossa (Balb/c) subcutaneouly,to obtain post-passage carcino-tissue and raise on mice livers. All animals were divided into 4 groups,10 mice each group: control group,low-AHCSE group(0.5 mg/kg),middle -AHCSE group(1.0 mg/kg) and high-AHCSE group(2.0 mg/kg). Different dosages of AHCSE were injected via vena caudalis every three days for three times. To explore therapic efficacy of different dosages of AHCSE on the basis of percent inhibition of neoplastic weight and positive cells of P53 and C-MYC. RESULTS:The experiment of aniso-dosage of AHCSE indicates, percent inhibition of tumor(PIT) was 35.57% in low-AHCSE group(0.5 mg/kg), the PIT in the middle-dosage group(1.0 mg/kg) was 50.38% and in high-AHCSE group (2.0 mg/kg) PIT was 53.89%. The expression of P53 protein was 64,51 and 45 and the expression of C-MYC protein was 46,38 and 34 in the three dosages groups.Inhibitory effect on tumor was significantly in middle -AHCSE and high-AHCSE. CONCLUSION: AHCSE has the significantly inhibitory effect on tumor in dose dependent. AHCSE may inhibit the tumor via down regulation the expression of P53, C-MYC protein.