Adenovirus-mediated anti-AEG-1 ScFv expression driven by stathmin promoter inhibits tumor growth in cervical cancer

作者: Min Long , Fang Lin , Xi Wang , Xi Chen , Li Liu

DOI: 10.1186/S12935-020-1159-5

关键词:

摘要: Background Astrocyte-elevated gene-1 (AEG-1) is over-expressed in many cancer cells and has multiple key functions tumor initiation progression. Currently, targeted-AEG-1 siRNA one of the most common techniques to down-regulate AEG-1 expression, but lack specificity available delivery system make it difficult enter clinical trials. Methods In this study, we creatively developed an adenovirus-mediated anti-AEG-1 single-chain antibody fragment (ScFv) expression driven by a specific promoter, experimented with human cervical carcinoma investigate effect on tumor's proliferation apoptosis. Results The results showed that HeLa SiHa treated recombinant ScFv adenovirus not only inhibited cell growth, induced apoptosis both vitro vivo. Furthermore, also observed expressions several apoptosis-related genes like Akt 1 c-Myc decreased, while NF-κB (p65) cleaved caspase 3 increased protein levels Conclusion We concluded stathmin promoter-driving adenoviral may be breakthrough for its dual-specificity, serve as adjuvant therapy method treatment cancers.

参考文章(27)
Chenchen Yang, Shutao Zheng, Qing Liu, Tao Liu, Mang Lu, Fang Dai, Xiangpeng Gao, Ilyar Sheyhidin, Xiaomei Lu, Metadherin is required for the proliferation, migration, and invasion of esophageal squamous cell carcinoma and its meta-analysis Translational Research. ,vol. 166, pp. 614- 626.e2 ,(2015) , 10.1016/J.TRSL.2015.05.004
Guoliang Yang, Lianhua Zhang, Shilong Lin, Linfeng Li, Mengyao Liu, Haige Chen, Ming Cao, Dongming Liu, Yi-ran Huang, Juanjie Bo, None, AEG-1 is associated with tumor progression in nonmuscle-invasive bladder cancer. Medical Oncology. ,vol. 31, pp. 986- ,(2014) , 10.1007/S12032-014-0986-4
Takehiko Yokobori, Koshi Mimori, Masaaki Iwatsuki, Hideshi Ishii, Ichiro Onoyama, Takeo Fukagawa, Hiroyuki Kuwano, Keiichi I. Nakayama, Masaki Mori, p53-Altered FBXW7 expression determines poor prognosis in gastric cancer cases Cancer Research. ,vol. 69, pp. 3788- 3794 ,(2009) , 10.1158/0008-5472.CAN-08-2846
Ke Dong, Rui Wang, Xi Wang, Fang Lin, Jian-Jun Shen, Ping Gao, Hui-Zhong Zhang, Tumor-specific RNAi targeting eIF4E suppresses tumor growth, induces apoptosis and enhances cisplatin cytotoxicity in human breast carcinoma cells. Breast Cancer Research and Treatment. ,vol. 113, pp. 443- 456 ,(2009) , 10.1007/S10549-008-9956-X
MIN LONG, KE DONG, PING GAO, XI WANG, LI LIU, SHUHUI YANG, FANG LIN, JUNXIA WEI, HUIZHONG ZHANG, Overexpression of astrocyte-elevated gene-1 is associated with cervical carcinoma progression and angiogenesis Oncology Reports. ,vol. 30, pp. 1414- 1422 ,(2013) , 10.3892/OR.2013.2598
Luni Emdad, Bin Hu, Swadesh K Das, Devanand Sarkar, Paul B Fisher, AEG-1-AKT2: A novel complex controlling the aggressiveness of glioblastoma. Molecular and Cellular Oncology. ,vol. 2, ,(2015) , 10.4161/23723556.2014.995008
S-G Lee, Z-Z Su, L Emdad, D Sarkar, T F Franke, P B Fisher, Astrocyte elevated gene-1 activates cell survival pathways through PI3K-Akt signaling Oncogene. ,vol. 27, pp. 1114- 1121 ,(2008) , 10.1038/SJ.ONC.1210713
Min Long, Miaowang Hao, Ke Dong, Jianjun Shen, Xi Wang, Fang Lin, Li Liu, Junxia Wei, Yingmin Liang, Jian Yang, Fangna Gu, Huizhong Zhang, AEG-1 overexpression is essential for maintenance of malignant state in human AML cells via up-regulation of Akt1 mediated by AURKA activation. Cellular Signalling. ,vol. 25, pp. 1438- 1446 ,(2013) , 10.1016/J.CELLSIG.2013.03.001
Huilin Zhang, Yuan Mao, Feng Zhang, Chunping Ye, Hua Tong, Yiping Su, Jin Zhu, The inhibitory effect of a new scFv/tP protein as siRNA delivery system to target hWAPL in cervical carcinoma Molecular and Cellular Biochemistry. ,vol. 391, pp. 77- 84 ,(2014) , 10.1007/S11010-014-1989-3