大鼠肝細胞癌變過程中survivin與livin的動態表達及相關性研究

李豐+王煒+姜開文+等

廣州醫科大學附屬第一醫院肝膽外科，廣東廣州 510000

[摘要] 目的 探討大鼠肝細胞癌變過程中survivin與livin的動態表達及其二者的相互關系。 方法 隨機將100只SD大鼠分為模型組與對照組各50只，模型組大鼠給予0.01%DEN自由飲用18周誘導大鼠肝癌模型，對照組大鼠常規自由飲水，于4、8、12、16、18周分別處死模型組10只，對照組10只。采用免疫組化、RT-PCR、Western bolt法檢測survivin和livin的表達。 結果 免疫組化結果顯示：模型組大鼠survivin、livin表達總陽性率分別為82%（41/50）、86%（43/50），survivin與livin都表達于肝癌組織及癌旁肝組織中，且二者的表達重疊，Spearman相關分析表明，二者的表達有相關性（r=0.9027，P < 0.05）。RT-PCR檢測結果顯示，肝癌組織中均有survivin mRNA和livin mRNA表達，隨著肝癌程度的加重而增加，與對照組肝組織比較，差異有統計學意義（P < 0.05）。Western blot結果顯示，survivin、livin的表達隨著肝癌程度的加重而增加，對照組肝組織比較，差異有統計學意義（P < 0.05）。 結論 survivin、livin在肝癌組織中高表達，且二者的表達密切相關，為肝細胞癌的臨床治療以及預后提供理論依據。

[關鍵詞] 大鼠；肝細胞癌；Survivin；Livin

[中圖分類號] R735.7 [文獻標識碼] A [文章編號] 1673-7210（2014）03（b）-0027-04

Dynamic expression and correlation of survivin and livin during hepatocellular carcinogenesis in rats

LI Feng WANG Wei JIANG Kaiwen ZHANG Longxin

Department of Hepatobiliary Surgery， the First Affiliated Hospital of Guangzhou Medical University， Guangdong Province， Guangzhou 510000， China

[Abstract] Objective To determine the dynamic expression and correlation of survivin and livin during hepatocellular carcinogenesis in rats. Methods 100 SD rats were divided into model group and control group with 50 rats in each group. Rats in the model group were given 0.01%DEN for drink induced model of liver cancer， while rats in the control group were given conventional water for drink. 10 rats in model group and control group were killed at 4， 8， 12， 16， 18 weeks respectively. Survivin and livin were measured by immunohistochemistry， RT-PCR， Western bolt. Results The results of immunohistochemistry showed that the total positive rates of survivin and livin were 82% （41/50）， 86% （43/50） in the model group， survivin and livin expressed in hepatic cellular cancer tissues and para-carcinoma tissue， the expression of them was overlapping. Spearman correlation analysis showed that the correlation between them was positive （r=0.9027， P < 0.05）. The results of RT-PCR showed that survivin mRNA and livin mRNA were expressed in hepatic cellular cancer tissues， increased with the liver cancer degree， compared with the control group， the difference was statistically significant （P < 0.05） .The results of Western blot showed that the expression of survivin and livin increased with the increase of hepatocellular carcinoma of liver tissue. There was statistically significant difference compared with the control group （P < 0.05）. Conclusion Survivin and livin are highly expressed in hepatic celluar Cancer tissues， and the expression of them are closely related. The results may provide a theoretical basis for the clinical treatment and prognosis of hepatocellular carcinoma.

[Key words] Rat； Hepatocellular carcinoma； Survivin； Livin

肝細胞癌（HCC）是臨床中常見的腫瘤，大部分進展期的病例缺乏有效的臨床治療，日益受到重視[1]。無限的細胞增殖和損傷凋亡的不平衡是HCC重要的特征[2]。IAP家族是重要的凋亡抑制因子。目前已發現8種IAPs，作為家族的新成員，survivin被認為在腫瘤的發生、發展中扮演重要角色；livin的研究則剛剛開始，其在肝腫瘤組織中的表達研究更不完善，在我國鮮有livin在肝癌組織中的研究報道。本文用免疫組化、Western bolt、RT-PCR法檢測抗凋亡蛋白livin、survivin蛋白和mRNA在肝癌組織中的表達，探討二者之間相互關系，從而為臨床診斷和肝癌的治療提供理論依據。……