Wu Sufang, Meng Li, Wang Shixuan, Wang Wei, Xi Ling, Tian Xun, Chen Gang, Wu Ying, Zhou Jianfeng, Xu Gang, Lu Yunping, Ma Ding
Cancer Biology Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, Republic of China.
Clin Cancer Res. 2006 Apr 1;12(7 Pt 1):2032-7. doi: 10.1158/1078-0432.CCR-05-2567.
Human papillomavirus (HPV) infection is the most important risk factor for the development of cervical cancer. The oncogene E7 from high-risk HPV strains has the ability to immortalize epithelial cells and increase cellular transformation in culture. In this study, we explored the possibility of preventing cervical cancer growth by inhibiting HPV16 E7 expression through gene transfer of an antisense construct. A recombinant adeno-associated virus (rAAV) vector was chosen for the transfer, based on its transfection efficiency, in vivo stability, and lack of detectable pathology. In vitro transfer of an rAAV vector expressing antisense HPV16 E7 (AAV-HPV16E7AS) inhibited cell proliferation, induced apoptosis, reduced cell migration, and restrained in vivo proliferation of HPV16/HPV18-positive cervical cancer CaSki cells. These results indicate that down-regulation of HPV16 E7 with antisense RNA is beneficial in reducing the tumorigenicity of CaSki cells, and rAAV vectors ought to be a new efficient approach for delivering the expression of therapeutic genes.
人乳头瘤病毒（HPV）感染是宫颈癌发生的最重要风险因素。高危HPV毒株的癌基因E7具有使上皮细胞永生化并增加培养中细胞转化的能力。在本研究中，我们探讨了通过反义构建体的基因转移抑制HPV16 E7表达来预防宫颈癌生长的可能性。基于其转染效率、体内稳定性以及缺乏可检测到的病理学特征，选择了重组腺相关病毒（rAAV）载体进行转移。表达反义HPV16 E7的rAAV载体（AAV-HPV16E7AS）的体外转移抑制了细胞增殖、诱导了凋亡、减少了细胞迁移，并抑制了HPV16/HPV18阳性宫颈癌CaSki细胞的体内增殖。这些结果表明，用反义RNA下调HPV16 E7有利于降低CaSki细胞的致瘤性，并且rAAV载体应该是一种递送治疗基因表达的新的有效方法。
