重组腺相关病毒介导TRAIL对卵巢癌裸鼠肝转移的抑制作用的实验研究

Studies of inhibitory effect of recombined adeno - associated virus mediated gene transfer of tumor necrosis factor related apoptosis inducing ligand on nude mice liver metastases of ovarian cancer

目的探讨重组腺相关病毒介导TRAIL对卵巢癌裸鼠肝转移的抑制作用。方法构建卵巢癌裸鼠肝转移模型。选择重组腺相关病毒rAAV—PEG—sTRAIL治疗，将裸鼠分为TRAIL治疗组和对照组，治疗6w后，观察肝转移率和肝转移结节数；Tunnel法分析TRAIL对肿瘤细胞的凋亡诱导情况。结果全身系统性给予重组腺相关病毒介导TRAIL后，治疗组和对照组相比转移率低，肝转移结节数目少，差异有统计学意义（p〈0．05）；Tunnel法分析TRAIL可诱导肿瘤细胞凋亡。结论重组腺相关病毒介导TRAIL可抑制卵巢癌裸鼠肝的转移生长，TRAIL用于卵巢癌肝转移的基因治疗中具有较好的应用前景。

ObjectiveTo investigate the inhibitory effect of the recombined adeno -associated virus encoding tumor necrosis factor related apoptosis inducing ligand （TRAIL） gene on nude mice liver metastases of human ovarian cancer. Methods Model of liver metastases was generated by injection of ovarian carcinoma cells SKOV3 into the abdomen of nude mice, and were randomly assigned to three groups： the TRAIL treatment group, which were treated with the recombined adeno -associated virus （rAAV） vector encoding soluble TRAIL gene by injecting from the tail vain and the two control groups, which was injected with rAAV - PEG - EGFP vector or PBS. After 6 weeks treatment, the occurrence of liver metastases and number of metastatic nodus were examined by HE staining ; tumor cell apoptosis was measured by TUNEL. Results Histological analysis showed rAAV - PEG - TRAIL treatment has significant inhibitory effects on intrahepatic tumor growth as seen by lower occurrence of hepatic metastases and less numbers of metastastic nodus compared with the control groups （p 〈 0.05 ）. TUNEL analysis demonstrated significant induction of tumor cell specific apoptosis. Conclusions rAAV - PEG - TRAIL has significant inhibitory effect on tumor growth of intrahepatic metastases from ovarian cancer, making it an ideal candidate of new gene therapy for liver metastases of ovarian cancer.