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内皮祖细胞介导的胞嘧啶脱氨酶与内皮抑素融合基因对肝癌的基因治疗

Gene Therapy with Cytosine Deaminase and Endostatin Fusion Gene Mediated by Endothelial Progenitor Cells in Hepatomas.

作者信息

Zhang Yue-Lin, Zhou Tan-Yang, Ai Jing, Chen Sheng-Qun, Chen Feng, Nie Chun-Hui, Chen Xin-Hua, Zhou Guan-Hui, Wang Hong-Liang, Zhu Tong-Yin, Wang Bao-Quan, Yu Zi-Niu, Jing Li, Wu Li-Ming, Zheng Shu-Sen, Sun Jun-Hui

机构信息

Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, People's Republic of China.

Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, Zhejiang Province, People's Republic of China.

出版信息

Cancer Manag Res. 2020 Apr 30;12:3023-3031. doi: 10.2147/CMAR.S245998. eCollection 2020.

Abstract

PURPOSE

Gene-targeting therapy provides a novel therapeutic approach for tumor treatment using genetically modified endothelial progenitor cells (EPCs) as cellular carriers. This study applied EPCs armed with cytosine deaminase (CD) and endostatin (ES) fusion gene in liver cancer to explore its therapeutic effect.

MATERIALS AND METHODS

EPCs from heart blood of male BALB/c nude mice were cultured and transfected with CD and ES fusion gene. Subsequently, these genetically modified cells were injected into mice bearing hepatoma through their tail veins. The tumor volumes and cell apoptosis were followed up.

RESULTS

Tumor volume in the group injected CD/ES-EPCs greatly decreased. The positive rate of VEGF and CD31 in the tumor tissue was lowest in the CD/ES-EPC group. Furthermore, the number of apoptotic cells was highest in the CD/ES-EPC group.

CONCLUSION

The EPCs transfected with CD/ES inhibited tumor growth and preferentially induced tumor cell apoptosis, providing a novel methodology for cancer-targeting therapy.

摘要

目的

基因靶向治疗提供了一种新的肿瘤治疗方法,即利用基因改造的内皮祖细胞(EPCs)作为细胞载体。本研究将携带胞嘧啶脱氨酶(CD)和内皮抑素(ES)融合基因的EPCs应用于肝癌治疗,以探索其治疗效果。

材料与方法

从雄性BALB/c裸鼠心脏血液中分离培养EPCs,并转染CD和ES融合基因。随后,将这些基因改造的细胞通过尾静脉注射到荷肝癌小鼠体内。对肿瘤体积和细胞凋亡情况进行随访。

结果

注射CD/ES-EPCs组的肿瘤体积显著减小。CD/ES-EPC组肿瘤组织中VEGF和CD31的阳性率最低。此外,CD/ES-EPC组的凋亡细胞数量最多。

结论

转染CD/ES的EPCs抑制肿瘤生长并优先诱导肿瘤细胞凋亡,为癌症靶向治疗提供了一种新方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0db/7198450/d7ce92c9ff3a/CMAR-12-3023-g0001.jpg

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