溶瘤腺病毒靶向杀灭葡萄膜黑色素瘤的实验研究

Viral Therapy Using the Oncolytic Adenovirus H101 to Treat Uveal Melanoma

葡萄膜黑色素瘤是成人最严重的原发性恶性肿瘤之一.传统的治疗方法,包括手术、放射治疗和化学治疗效果都不是很理想.溶瘤腺病毒H101,能够特异性地在p53突变的肿瘤细胞中复制并杀伤肿瘤细胞,同时对正常细胞影响较少,且已由中国国家食品药品监督管理总局批准上市.为了研究H101对葡萄膜黑色素瘤的治疗效果,通过体外感染葡萄膜黑色素瘤细胞,发现H101能够显著抑制葡萄膜黑色素瘤细胞的增殖并促进细胞凋亡,抑制细胞周期,而对正常的ARPE-19细胞没有影响.在体内实验中,建立了SP6.5细胞的荷瘤小鼠模型,在H101治疗后抑制了肿瘤的生长,延长了动物寿命.上述结果表明,溶瘤腺病毒H101治疗葡萄膜黑色素瘤是一种可行的方法.

Uveal melanoma is the most serious primary intraocular malignancy in adults. Traditional approaches to treating uveal melanoma, including surgery, radiotherapy and chemotherapy, are insufficient. The oncolytic adenovirus H101 specifically replicates in and kills p53-mutant tumour cells while sparing normal cells and has been approved for use by the China Food and Drug Administration. To investigate the effect of treating uveal melanoma with H101, we infected specific uveal melanoma cell lines in vitro and observed significant cell growth inhibition, apoptosis and cell cycle arrest; the treatment was innocuous in the ARPE-19 normal cell line. In vivo, an intratumoural injection of H101 inhibited tumour growth and prolonged animal survival in the SP6.5 turnout xenograft mouse model. These results indicated that viral therapy using the oncolytic adenovirus H101 is feasible and promising for the treatment of uveal melanoma.