High-risk human papillomavirus (hr-HPV) E6 and E7 oncogenes are associated with resistance to radiotherapy in cervical cancer. Efforts have been taken to employ HPV E2, a crucial negative transcriptional modulator of HPV E6 and E7 oncogenes, and also an apoptosis-inducing agent, for therapeutic intervention. Despite being conceptually attractive, the potency and feasibility of current hr-HPV E2-based therapies remain limited. Here, we designed a novel recombinant adenovirus, named M5, with a 27-bp deletion in E1A conserved region-2 by which to realize tumor-specific replication, and a total HPV type 16 (HPV16) E2 gene complementary DNA inserted into the E3 coding region. In this design, M5 exploited the adenovirus E3 promoters to express HPV16 E2 gene in a viral replication-dependent manner and preferentially silenced the hr-HPV E6 and E7 oncogenes in HPV-positive cervical cancer cells. In vitro and in vivo assays confirmed that M5 exhibited potent antitumoral efficacy. Moreover, the effects of combined treatment with M5 and radiation treatment resulted in synergistically enhanced potency (P<0.01). The increase in killing efficacy of M5 was also found in HPV-negative cervical cancer cells, for which the pro-apoptotic activity of HPV16 E2 was thus responsible. Our results indicated that the use of M5 that locally delivers HPV16 E2 to cancers has broad therapeutic windows and that the combination therapy with radiation for cervical cancer will be the more effective way of improving survival. Cancer Gene Therapy (2011) 18, 825-836; doi:10.1038/cgt.2011.53; published online 19 August 2011
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81072132, 30973184, 30901586]; PhD Programs Foundation of Ministry of Education of ChinaMinistry of Education, China [200804871095]; Natural Science Foundation of Hubei Province of ChinaNatural Science Foundation of Hubei Province [2008CDB213]; National Science and Technology Support Plan [2008BAI57B01]
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外文
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出版当年[2010]版：
大类|3 区医学
小类|3 区生物工程与应用微生物3 区遗传学3 区医学：研究与实验3 区肿瘤学
最新[2025]版：
大类|3 区医学
小类|3 区生物工程与应用微生物3 区遗传学3 区医学：研究与实验4 区肿瘤学
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出版当年[2009]版：
Q2ONCOLOGYQ2MEDICINE, RESEARCH & EXPERIMENTALQ2BIOTECHNOLOGY & APPLIED MICROBIOLOGYQ2GENETICS & HEREDITY
最新[2023]版：
Q1BIOTECHNOLOGY & APPLIED MICROBIOLOGYQ1GENETICS & HEREDITYQ1MEDICINE, RESEARCH & EXPERIMENTALQ1ONCOLOGY
第一作者单位：[1]Huazhong Univ Sci & Technol, Tongji Med Coll, Canc Biol Res Ctr, Tongji Hosp, Wuhan 430030, Hubei, Peoples R China;[2]So Med Univ, Nanfang Hosp, Dept Gynecol & Obstet, Guangzhou, Guangdong, Peoples R China;
共同第一作者：
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通讯机构：[1]Huazhong Univ Sci & Technol, Tongji Med Coll, Canc Biol Res Ctr, Tongji Hosp, Wuhan 430030, Hubei, Peoples R China;
推荐引用方式(GB/T 7714)：
Wang W.,Xia X.,Wang S.,et al.Oncolytic adenovirus armed with human papillomavirus E2 gene in combination with radiation demonstrates synergistic enhancements of antitumor efficacy[J].CANCER GENE THERAPY.2011,18(11):825-836.doi:10.1038/cgt.2011.53.
APA：
Wang, W.,Xia, X.,Wang, S.,Sima, N.,Li, Y....&Ma, D..(2011).Oncolytic adenovirus armed with human papillomavirus E2 gene in combination with radiation demonstrates synergistic enhancements of antitumor efficacy.CANCER GENE THERAPY,18,(11)
MLA：
Wang, W.,et al."Oncolytic adenovirus armed with human papillomavirus E2 gene in combination with radiation demonstrates synergistic enhancements of antitumor efficacy".CANCER GENE THERAPY 18..11(2011):825-836
