Beijing Tongren Hospital, Capital Medical University, Beijing, Ophthalmology & Visual Sciences Key Lab, Dongjiao Minxiang 1, Dongcheng District, Beijing 100730, China.
Brain Tumor Research Center, Beijing Laboratory of Biomedical Materials, Beijing Neurosurgical Institute, Department of Neurosurgery, Beijing Tiantan Hospital affiliated to Capital Medical University, Tiantan Xili 6, Dongcheng District, Beijing 100050, China.
Exp Eye Res. 2018 Jul;172:144-151. doi: 10.1016/j.exer.2018.04.009. Epub 2018 Apr 13.
Uveal melanoma (UM) is the most common primary intraocular tumor in adults, which has high frequency of metastasis to the liver, typically causing a fatal outcome. Chemo-resistance remains a major obstacle in the therapeutic approach to UM, leaving limited choice for treating UM. Other possible treatments have been explored but the results are yet to be evident. To improve therapy for UM, transcriptional suicide genes were transfected into the OCM-1 cell line. In the current study, OCM-1 cells transfected with lentiviral-meditated EGFP, cytosine deaminase (CD)/EGFP, and VP22-CD/EGFP were established. Of the three groups, we examined the cell growth in vitro and in vivo by using the MTT method with cell culture media and MRI in murine UM models. According to our results, the cell proliferation in the transfected CD/EGFP group was slower than the non-suicide gene group. The VP22-CD/EGFP group manifested superior cell cytotoxicity than the CD/EGFP group. Further analysis of MRI and fluorescent imaging of the murine UM model identified significant differences in tumor volume among the three groups. Collectively, our study demonstrated that CD/5-FC is a potent therapeutic approach for UM. With the efficacy of VP22, suicide gene-induced cytotoxicity was superior to applying CD alone. Taken together, we concluded that novel therapy with the VP22-CD suicide gene may further contribute to treatment of UM.
葡萄膜黑色素瘤（UM）是成年人中最常见的原发性眼内肿瘤，其向肝脏转移的频率很高，通常导致致命的后果。化疗耐药性仍然是 UM 治疗方法的主要障碍，这使得 UM 的治疗选择有限。已经探索了其他可能的治疗方法，但结果尚未显现。为了改善 UM 的治疗效果，将转录自杀基因转染到 OCM-1 细胞系中。在本研究中，建立了转染慢病毒介导的 EGFP、胞嘧啶脱氨酶（CD）/EGFP 和 VP22-CD/EGFP 的 OCM-1 细胞。在这三组中，我们通过使用细胞培养物中的 MTT 法和小鼠 UM 模型中的 MRI 检查了体外和体内的细胞生长。根据我们的结果，转染 CD/EGFP 组的细胞增殖比非自杀基因组慢。VP22-CD/EGFP 组的细胞毒性优于 CD/EGFP 组。对小鼠 UM 模型的 MRI 和荧光成像的进一步分析表明，三组之间的肿瘤体积存在显著差异。总之，我们的研究表明 CD/5-FC 是治疗 UM 的有效方法。VP22 的功效使自杀基因诱导的细胞毒性优于单独应用 CD。综上所述，我们得出结论，VP22-CD 自杀基因的新疗法可能进一步有助于 UM 的治疗。
