Potentiation of tumor radiotherapy by a radiation-inducible oncolytic and oncoapoptotic adenovirus in cervical cancer xenografts

作者：Wang, Haibo; Song, Xin; Zhang, He; Zhang, Jianjun; Shen, Xiaodi; Zhou, Yixiong; Fan, Xianqun; Dai, Liyan; Qian, Guanxiang; Hoffman, Andrew R; Hu, Ji Fan^*; Ge, Shengfang

来源：International Journal of Cancer, 2012, 130(2): 443-453.

DOI：10.1002/ijc.26013

• Egr-1 promoter
• TRAIL
• gene therapy
• radiotherapy
• tumor
• apoptosis
• adenovirus

The p53 tumor suppressor pathway is impaired in more than 90% of cervical cancers and cancer-derived cell lines as a result of infection by human papillomavirus (HPV). The HPV E6 oncoprotein forms complexes with p53 and promotes its degradation via ubiquitin-dependent mechanism. In our study, we attempted to improve the clinical outcomes of this combined therapy by modifying the p53-targeted adenovirus to become radiation-responsive. The antitumor adenovirus was constructed by inserting a radiation-responsive expression cassette composed of the promoter of early growth response-1 (Egr-1) and the proapoptotic protein TRAIL. We showed that the addition of adenovirus containing Egr-1/TRAIL significantly increased cell death and apoptosis caused by radiotherapy. In mice bearing xenograft tumors, intratumoral administration of the Egr-1/TRAIL adenovirus followed by radiation significantly reduced tumor growth and enhanced tumor survival. Our Egr-1/TRAIL adenoviral gene product may offer a novel one-two punch tumor therapy for cervical cancers not only by potentiating radiation treatment but also by preserving p53 defect-specific tumor killing of the oncolytic adenovirus.

• 出版日期2012-1-15
• 单位上海交通大学