榄香烯对肝癌H22细胞荷瘤小鼠的抑瘤作用及其可能机制

Antitumor effects and possible mechanism of elemene on expression in ascites hepatoma cell line H22

目的研究榄香烯对肝癌H22细胞荷瘤小鼠的抑瘤作用及与c-Met磷酸化表达水平之间的关系。方法建立H22小鼠肝癌实体瘤模型。将60只H22肝癌实体瘤模型小鼠分为4组:100与50mg·kg^(-1)组、5-氟尿嘧啶组和生理盐水组各15只。药物注射30d后,通过测定荷瘤小鼠的瘤质量,计算抑瘤率;同时采用免疫组织化学和免疫荧光技术检测肿瘤组织和H22细胞中c-Met磷酸化的表达情况。结果 100mg·kg^(-1)榄香烯能使肝癌荷瘤小鼠的瘤质量减少,抑瘤率为41.6%。免疫组化结果显示100mg·kg^(-1)榄香烯组c-Met磷酸化表达显著增强,与生理盐水组相比差异有统计学意义(P<0.05);榄香烯组与5-Fu组比较,差异无统计学意义(P>0.05)。体外免疫荧光结果显示c-Met磷酸化表达程度随榄香烯药物作用时间增加而增强。结论榄香烯具有抗肿瘤作用,作用机制可能与能增强c-Met磷酸化的表达有关。

A/M To investigate the antitumor mechanism of elemene in ascites hepatoma cell line H22, and the relationship of it and the expression level of c-Met phosphorylation（pc-Met）. METHODS An experimental H22 hepato cellular carcinoma （HCC） xenograft transplantation model was induced after injecting ascites hepatoma cell line H22 into their right oxter, and sixty tumor-bearing mice were divided into 4 groups： 100 rag. kg-1 elemene group, 50 mg. kg-1 el emene group, 5-fluorouracil（5-Fu） positive group and normal saline （NS） group. After 30 d, tumor was obtained and the inhibitory rates of solid tumor were observed. The expression of pc-Met was examined by immunohistochemistry strain ing method in vivo and immunofluorescence technique in vitro. RESULTS The 100 rag＂ kg- 1 β-elemene-induced reduc tions of tumor weight were progressive during the period of the experiment. The inhibiting rate in 100 rag. kg- l elemene group was 41.6%, which was obviously higher than that in NS group （P 〈 0.05） . In the tumor tissues, both 100 nag. kg- 1 element group and 50 mg. kg- 1 element group had more positive pc-Met cells than that in NS group. Rank-sum test showed that expression of pc-Met was increased in the drug groups, the difference between the drug groups and NS group had statistical significance, but the differences between element groups and 5-Fu group （P 〉 0.05） had not statistical significance. After H22 cells were treated with various concentrations of the drugs, the expression of pc-Met was en hanced with increased time of drug action in vitro. CONCLUSION The mechanism of elemene significantly inhibiting effect on ascites hepatoma cell line H22 cells may be relative to the expression level of pc-Met.