去氢表雄酮通过调节丝／苏氨酸蛋白激酶信号传导通路抑制大鼠Morris肝细胞瘤生长  

The effect of DHEA on AKT signal pathway on transplanted Morris hepatomas in rats

作　　者：姜艳芳[1] 赵平伟[2] 秦俊杰[1] 李明辉[1] 松崎静司[3] 牛俊奇[1] 

机构地区：[1]吉林大学第一医院肝胆胰内科,长春130021 [2]吉林大学第四医院肝胆外科 [3]日本筑波大学消化内科

出　　处：《中华肝脏病杂志》2009年第9期679-682,共4页Chinese Journal of Hepatology

基　　金：吉林省科技厅国际合作项目（200507036）;国家留学基金委资助课题（21822067）

摘　　要：目的探讨去氢表雄酮（DHEA）的体内抗癌作用及其机制。方法Buffalo大鼠21只随机分为空白对照组、肿瘤对照组（把Morris肝细胞瘤移植到大鼠的两肋皮下，建立Morris肝细胞瘤移植的Buffalo大鼠的体内模型，基础饲料喂养）、DHEA肿瘤组（建立Morris肝细胞瘤移植模型后，在喂养的基础饲料中添加DHEA）和去氢表雄酮硫酸酯（DHEAs）肿瘤组（建立Morris肝细胞瘤移植模型后，在喂养的基础饲料中添加DHEAs）。分别喂养4周后，Westernblot和免疫组织化学方法检测磷酸化丝／苏氨酸蛋白激酶（Akt）、PTEN等蛋白的表达，流式细胞术检测大鼠CD3、CD4、CD8和CD4／CD8。单因素方差分析对数据进行处理。结果DHEA肿瘤组的肝细胞瘤的质量为（8．31±0．61）g，较肿瘤对照组的（14．57±0．56）g显著减轻（P〈0．05）。Westernblot及免疫组织化学染色结果显示，DHEA肿瘤组的磷酸化Akt蛋白表达量降低，而PTEN蛋白表达增强；CD3阳性细胞百分率（74．97％±8．29％）较肿瘤对照组（56．45％±6．12％）明显提高（t=4．92，P〈0．05），CD4／CD8比值升高（1．75±0．22）。而DHEAs肿瘤组CD3阳性细胞百分率（60．04％±6．69％）较空白对照组（75．38％±9．76％）明显降低（t=3．87，P〈0．05），同时CD4／CD8比值也降低（1．48±0．56）。结论DHEA对体内的肿瘤具有明显的抑制作用，此作用可能是其通过调节体内的Akt信号传导通路和免疫功能来完成的。Objective To investigate the inhibitory effect of dehydroepaimdrosterone （DHEA） on the growth of transplatnted Morris hepatomas （7288CTC） in vivo in rats. Methods 21 Buffalo rats were randomly devided into 4 groups, including one blank control group （n = 5）, one group for tumor-bearing control （n = 6）, and 2 experimental groups with DHEA （n = 6） or DHEA-s （n = 4）. DHEA or DHEA-s was fed to the rats for 4 weeks immediately after Morris hepatomas （7288CTC） was implanted in both flanks. Pheno- types of the spleen lymphocytes were examined by flow cytometry, Akt and PTEN expression in tumor cells was detected by Western blot and immunohistochemistry. Results Tumor weights of DHEA treated group were less than those of the control （P 〈 0.05）, the inhibitory rate was 43%. The results of Western blot and immunohistochemistry showed that in DHEA tumor group,the expression of phosphorilated Akt protein was decreased, the expression of PTEN was enhanced, the percentage of CD3 positive cells and the ratio of CD4/ CD8 were increased （P 〈 0.05）. Conclusion DHEA can inhibit tumor growth, possibly via the inhibition of the Akt signaling pathway as well as modulating the immune function.

关 键 词：肝肿瘤 基因 抑制 肿瘤 蛋白质丝氨酸苏氨酸激酶 去氢表雄酮 PTEN 

分 类 号：R735.7[医药卫生—肿瘤]