Radiation‐inducible human tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL) gene therapy: a novel treatment for radioresistant uveal melanoma
Radiation‐inducible human tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL) gene therapy: a novel treatment for radioresistant uveal melanoma
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DOI：
10.1111/j.1755-148x.2010.00729.x
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发表时间：
2010-10
影响因子：
4.3
通讯作者：
Yixiong Zhou;Xin Song;Renbing Jia;Haibo Wang;Liyan Dai;Xiaofan Xu;P. Gu;S. Ge;Xianqun Fan
中科院分区：
文献类型：
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作者：
Yixiong Zhou;Xin Song;Renbing Jia;Haibo Wang;Liyan Dai;Xiaofan Xu;P. Gu;S. Ge;Xianqun Fan
葡萄膜黑色素瘤(UM)是最耐药的癌症之一。放射治疗是大多数UM的首选治疗方法。然而，一些UM细胞，如SP6.5或OM431细胞系，相对耐辐射。在这项研究中，我们试图使用腺病毒放射诱导基因治疗系统来改进目前的UM治疗。构建含辐射诱导早期生长反应基因1(Egr1)启动子和抗癌肿瘤坏死因子相关凋亡诱导配体(TRAIL)基因的抗肿瘤腺病毒。我们证明UM SP6.5和OM431细胞系对TRAIL诱导的抗肿瘤作用敏感。含Egr1/TRAIL的腺病毒(Ad-ET)治疗组放疗后TRAIL表达增强，而Ad-ET明显增加放疗所致的细胞死亡和细胞凋亡。在荷瘤小鼠的病理肿瘤切片中可检测到凋亡细胞。腺病毒Ad-ET联合放射治疗明显抑制肿瘤生长，与其他治疗组比较有显著差异(P<；0.01)。我们的发现表明，放射反应基因治疗有可能成为一种更有效和更特异的治疗UM的方法，因为治疗基因可以在空间或时间上受到外源辐射的控制。
Uveal melanoma (UM) is one of the most therapy‐resistant cancers. Radiotherapy is the preferred treatment for most cases of UM. However, some UM cells, such as the SP6.5 or OM431 cell lines, are relatively radioresistant. In this study, we attempted to improve the current UM therapy using an adenovirus radio‐inducible gene therapy system. The antitumor adenovirus was constructed by inclusion of the radiation‐inducible early growth response gene 1 (EGR1) promoter and the anticancer tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL) gene. We demonstrated that the UM SP6.5 and OM431 cell lines were susceptible to the TRAIL‐induced antitumor effect. TRAIL expression was enhanced in the adenovirus containing EGR1/TRAIL (Ad‐ET) treatment group by radiotherapy, whereas Ad‐ET significantly increased cell death and apoptosis caused by radiotherapy. In mice bearing xenograft tumors, apoptotic cells were detected in pathological tumor sections. Adenovirus Ad‐ET combined with radiation therapy significantly inhibited tumor growth compared with the other treatment groups (P < 0.01). Our findings indicate that radioresponsive gene therapy has the potential to be a more effective and specific therapy for UM because the therapeutic gene can be spatially or temporally controlled by exogenous radiation.