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【medical-news】子宫颈癌基因治疗:条件复制性E1B缺
Cancer Gene Therapy (2008) 15, 526–534; doi:10.1038/cgt.2008.37; published online 23 May 2008
Conditionally replicating E1B-deleted adenovirus driven by the squamous cell carcinoma antigen 2 promoter for uterine cervical cancer therapy
K-F Hsu, C-L Wu, S-C Huang, J-L Hsieh, Y-S Huang, Y-F Chen, M-R Shen, W-J Chung, C-Y Chou and A-L Shiau
Cervical cancer is the second most common type of malignant tumor among women worldwide. When the disease is confined locally, it can be controlled with surgical resection and radiotherapy. However, patients with recurrent or metastatic disease often have a poor prognosis. Measurement of serum levels of squamous cell carcinoma (SCC) antigens has been widely used as serological markers for SCC of uterine cervix. Recently, it has been demonstrated that cervical cancer patients with elevated squamous cell carcinoma antigen-2 (SCCA2) expression in tumor cells carry a poor prognosis. Here, by using a luciferase reporter assay, we show that SCCA2 promoter was active in SCCA2-producing human cervical cancer cell lines, including Cx, Cxwj, SiHa and HeLa cells, but relatively quiescent in normal cervical epithelial cells. We then developed a conditionally replicating adenovirus, designated Ad-KFH, under the transcriptional control of the SCCA2 promoter. This E1B-55 kDa-deleted oncolytic adenovirus replicated specifically in and lysed SCCA2-producing cervical cancer cells. Furthermore, in a peritoneal metastatic tumor model, Ad-KFH retarded Cxwj tumor growth in NOD/severe combined immunodeficient mice and prolonged survival of tumor-bearing mice, especially when combined with cisplatin. These results suggest that Ad-KFH may provide a new strategy of gene therapy for advanced or recurrent uterine cervical cancer.
Keywords:
oncolytic virus, SCC, cervical cancer
子宫颈癌基因治疗
条件复制性E1B缺陷腺病毒加入SCCA2启动子可用于宫颈癌的基因治疗
子宫颈癌在国际上常见女性恶性肿瘤中位居第二位。如果肿瘤限于局部，可用手术切除联合放射疗法控制癌症的发展。但是，复发性或转移性子宫颈癌患者预后都很差。测定血清鳞状细胞癌抗原被广泛用作宫颈鳞状细胞癌的血清学标志。最近研究表明，宫颈癌病人检查出肿瘤细胞高表达SCCA2（鳞状细胞癌抗原-2）则预后较差。应用萤光素酶报告基因，我们发现SCCA2启动子在产生SCCA2的人宫颈癌细胞系较活跃，如Cx，Cxwj，SiHa，HeLa细胞系，但在正常宫颈上皮细胞则相对静止。随后我们设计了一种条件性复制的腺病毒，命名为Ad-KFH，使之在SCCA2启动子转录控制之下。这种病毒敲除了E1B-55 kDa片段的表达，成为一种溶瘤病毒，仅在产生SCCA2的宫颈癌细胞中进行复制，并且溶解宫颈癌细胞。另外，Ad-KFH使得NOD/SCID小鼠的Cxwj腹腔转移瘤细胞生长延迟，延长了荷瘤小鼠的生存时间，尤其是与顺铂联合作用时。这些结果表明Ad-KFH为晚期和复发性宫颈癌提供了治疗的新策略。
主题词：
溶瘤病毒，鳞状细胞癌，宫颈癌 [标签:content1][标签:content2]
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作者:admin@医学,生命科学 2011-10-14 17:18
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