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RGD-rAAV2提高卵巢癌细胞体外基因转导效率的研究 被引量：1

RGD-modified rAAV2 Mutant Vectors Enhance Gene Transduction in Ovarian Cancer Cell Lines
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摘要 目的进一步证实精氨酸-甘氨酸-天冬氨酸-重组腺相关病毒2(RGD-rAAV2)基因表达系统靶向卵巢肿瘤的能力。方法用流式细胞仪(FACS)检测6种卵巢癌细胞株的硫酸肝素蛋白多糖(HSPG)、整合素(integrin)αvβ3和integrinαvβ5的表达;以及野生型腺相关病毒2(wt-AAV2)对上述卵巢癌细胞感染并介导基因转导的能力;通过配体竞争结合实验进一步验证突变体RGD-rAAV2基因转导的特异性。结果wt-AAV2感染不同卵巢癌细胞的能力各有不同;卵巢癌细胞表达HSPG水平差异很大,而80%卵巢癌细胞表达integrinαvβ3或(和)integrinαvβ5;RGD-rAAV2病毒载体可以有效地感染对wt-rAAV2耐受的卵巢癌细胞SKOV-3ip并介导基因的表达,该效果是非HSPG依赖性的。结论RGD-rAAV2病毒载体具有较高的卵巢肿瘤靶向性,为卵巢癌基因靶向治疗提供了一种新的策略。 Objective To further investigate the specific gene transduction mediated by RGD-rAAV2 mutant vector in ovarian cancer cell lines. Methods The expression of HSPG and the integrin αvβ3 and αvβ5 was detected by using FACS on 6 human ovarian cancer cell lines （ PA-1, OV-3, OV-4, OVCAR-3, SKOV-3ip and Hey）. The gene transduction efficiencies mediated by wild type rAAV2 in different ovarian cancer cell lines were evaluated by FACS. Ligands competitive binding experiment was used to assess whether RGD-rAAV2 was able to mediate successfully gene transduction in wt-rAAV2 resistant cell llne SKOV- 3ip. Results Wild type rAAV2 variably transduced the different ovarian cancer cell lines. HSPG expression varied eonsidera bly among the six tested ovarian cancer cell lines, and 80% of cell lines expressed moderate integrin αvβ3 and αvβ5. RGD- rAAV2 exerted more effective infection and higher gene transduction in SKOV-3ip than wt rAAV2. Conclusion Integrin-retargeted RGD-rAAV2 showed higher efficacy in gene transduction which was in-dependent of HSPG, which provided its application feasibility in ovarian cancer gene therapy in vivo.
作者 方光光 王迪 唐良振 石文芳
机构地区 深圳市第二人民医院妇产科 华中科技大学同济医学院基础医学院免疫学系 武汉市第二医院普外科
出处 《华中科技大学学报（医学版）》 CAS CSCD 北大核心 2006年第2期209-212,共4页 Acta Medicinae Universitatis Scientiae et Technologiae Huazhong
关键词 卵巢癌 精氨酸-甘氨酸-天冬氨酸 腺相关病毒 基因转导 ovarian carcinoma Arg-Gly-Asp adeno-associated virus gene transduction
分类号 R737.31 [医药卫生—肿瘤]
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参考文献10

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同被引文献42

  • 1刘昭飞,贾兵,史继云,杨志,赵慧云,王凡.^(99)Tc^m-RGD环肽二聚体的制备及其体内外评价[J].中华核医学杂志,2007,27(4):205-209. 被引量：18
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华中科技大学学报（医学版）
2006年 第2期

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