Department of Ophthalmology, Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Cancer Biol Ther. 2012 Jan 15;13(2):77-84. doi: 10.4161/cbt.13.2.18436.
Uveal melanoma is the most common primary intraocular malignancy in adults; however, current therapeutic modalities, including chemotherapy, have not been successful. Oncolytic viruses serve as an emerging gene therapy tool for cancer treatment because they specifically kill tumor cells while sparing normal cells. The oncolytic virus H101 has been approved by the Chinese State Food and Drug Administration for the treatment of certain malignancies. Unfortunately, the monotherapy of adenovirus has demonstrated limited efficacy in a clinical setting. Thus, novel treatment strategies in which an oncolytic virus is combined with existing chemicals are advancing toward potential clinical use. In this study, we chose the combination of oncolytic virus H101 and the alkylating agent dacarbazine (DTIC) to treat uveal melanoma cells in vitro. Our results demonstrated that the combination exerted a synergistic antitumor effect without enhanced toxicity to normal cells via a type of cell cycle block other than the induction of apoptosis. Further investigation is warranted to elucidate the specific underlying mechanisms of this co-treatment therapy. Our study suggests the viro-chemo combination therapy is feasible and is a potentially promising approach for the treatment of uveal melanoma.
葡萄膜黑色素瘤是成年人中最常见的原发性眼内恶性肿瘤；然而，包括化疗在内的当前治疗方法并不成功。溶瘤病毒作为癌症治疗的一种新兴基因治疗工具，因为它们可以特异性地杀死肿瘤细胞而不损伤正常细胞。溶瘤病毒 H101 已被中国国家食品药品监督管理局批准用于治疗某些恶性肿瘤。不幸的是，腺病毒的单一疗法在临床环境中显示出有限的疗效。因此，将溶瘤病毒与现有化学物质联合使用的新型治疗策略正在朝着潜在的临床应用方向发展。在这项研究中，我们选择了溶瘤病毒 H101 和烷化剂达卡巴嗪（DTIC）联合治疗体外葡萄膜黑色素瘤细胞。我们的结果表明，该联合治疗在不增加正常细胞毒性的情况下，通过一种不同于诱导细胞凋亡的细胞周期阻滞类型，发挥协同抗肿瘤作用。需要进一步研究来阐明这种联合治疗的具体潜在机制。我们的研究表明，病毒-化疗联合治疗是可行的，并且是治疗葡萄膜黑色素瘤的一种有前途的方法。
