腺病毒介导多基因对胆管癌细胞凋亡的诱导和肝细胞毒性损害

Effects of adenovirus mediated multigenes on the induction of apoptosis of cholangiocarcinoma cell line and the cytotoxicity of hepatocyte line

目的：研究腺病毒介导的多基因（ＧＭ－ＣＳＦ、Ｂ７－１、ｐ５３、ＩＬ－２）对胆管癌细胞系ＱＢＣ９３９ 凋亡的诱导作用和对正常肝细胞的作用。方法：应用ＴＵＮＥＬ细胞凋亡检测法和光镜观察，分析同时含ＧＭ－ＣＳＦ、Ｂ７－１、ｐ５３、ＩＬ－２ ４ 种目的基因的重组腺病毒载体（Ａｄ－ｍ ｕｌｔｉｇｅｎｅｓ）对胆管癌细胞系ＱＢＣ９３９ 和肝细胞系Ｌ０２的作用以及对大鼠肝脏的毒性损害。结果：Ａｄ－ｍｕｌｔｉｇｅｎｅｓ与化疗药物顺铂协同，能诱导３０％ 左右的ＱＢＣ９３９发生凋亡，并对肝细胞系Ｌ０２ 和大鼠肝细胞无明显毒性损害。结论：Ａｄ－ｍ ｕｌｔｉｇｅｎｅｓ能诱导胆管癌细胞ＱＢＣ９３９ 发生凋亡，且与化疗药物顺铂具有协同增强作用。初步分析对人肝细胞及大鼠肝脏无明显毒性损害，具有一定的临床应用前景。

Objective: To study the effects of adenovirus mediated GM CSF, B7 1, p53 and IL 2 on the induction of apoptosis of cholangiocarcinoma cell line QBC939 and on the cytotoxicity of hepatocyte line L02. Methods: After the construction of recombinant adenovirus containing human GM CSF, B7 1, p53 and IL 2 genes, their effects on apoptosis of human cholangiocarcinoma cell line QBC939 and on cytotoxicity of hepatocyte line L02 and the liver of rats were detected with TUNEL assay and optical microscopy. Results: Adeno virus mediated multigenes induced nearly 30% apoptosis of cholangiocarcinoma cell line QBC939 in combination with a chemotherapeutic agent cisplatin and showed no distinct cytotoxicity of hepatocyte line L02 and rat liver. Conclusion: Adenovirus mediated GM CSF, B7 1, p53 and IL 2 are able to induce 30% apoptosis of cholangiocarcinoma cell line and show no cytotoxicity of liver cells.