Pennant W A, An S, Gwak S-J, Choi S, Banh D T, Nguyen A B L, Song H Y, Ha Y, Park J-S
Spine and Spinal Cord Institute, Department of Neurosurgery, Yonsei University College of Medicine, Seoul, Republic of Korea.
Department of Chemistry, Seoul National University, Seoul, Republic of Korea.
Spinal Cord. 2014 Jan;52(1):3-8. doi: 10.1038/sc.2013.106. Epub 2013 Nov 5.
The objective of this study is to evaluate the safety and efficacy of a tumor-specific apoptosis-inducing gene, apoptin, as delivered by the non-viral carrier, PAM-RG4, in an animal model of spinal cord tumor.
Male Sprague-Dawley rats were given a 2.5-μl intramedullary injection of C6 glioma (100,000) cells and randomized into three groups (day 0). On day 5, animals received a 7.5-μl intramedullary injection of Dulbecco's modified Eagle's medium (Group 1; n=7), PAM-RG4/control gene polyplex (Group 2; n=7), or PAM-RG4/apoptin gene polyplex (Group 3; n=8). Hindlimb functional strength was assessed every other day for the duration of the study. The spinal cords of killed animals were collected and hematoxylin-eosin stained.
Following treatment, animals that received apoptin had significantly higher mean functional hindlimb scores than those of sham control animals, showing a level of preserved hindlimb function throughout the study. In addition, Group 1 (sham control) and Group 2 (control gene) animals had median survival scores lower than those of animals receiving apoptin. Histopathological analysis showed marked retardation of tumor progression in apoptin-treated animals compared with sham controls.
Our study suggests that apoptin is safe for use in the mammalian spinal cord as well as effective in slowing the progression of tumor growth in the spinal cord. The significant slowing of tumor progression, as manifested by the preserved hindlimb function, coupled with the reduction in tumor volume, shows local non-viral delivery of apoptin could serve as an emerging therapy for the treatment of intramedullary spinal cord tumors.
本研究的目的是评估由非病毒载体PAM-RG4递送的肿瘤特异性凋亡诱导基因apoptin在脊髓肿瘤动物模型中的安全性和有效性。
给雄性Sprague-Dawley大鼠进行2.5μl髓内注射C6胶质瘤（100,000）细胞，并随机分为三组（第0天）。在第5天，动物接受7.5μl髓内注射杜氏改良 Eagle培养基（第1组；n = 7）、PAM-RG4/对照基因多聚体（第2组；n = 7）或PAM-RG4/apoptin基因多聚体（第3组；n = 8）。在研究期间每隔一天评估后肢功能强度。收集处死动物的脊髓并进行苏木精-伊红染色。
治疗后，接受apoptin治疗的动物的平均后肢功能评分显著高于假手术对照动物，在整个研究过程中显示出一定程度的后肢功能保留。此外，第1组（假手术对照）和第2组（对照基因）动物的中位生存评分低于接受apoptin治疗的动物。组织病理学分析显示，与假手术对照相比，apoptin治疗的动物肿瘤进展明显迟缓。
我们的研究表明，apoptin在哺乳动物脊髓中使用是安全的，并且在减缓脊髓肿瘤生长进展方面有效。后肢功能保留所显示的肿瘤进展显著减缓，以及肿瘤体积的减小，表明局部非病毒递送apoptin可作为治疗脊髓髓内肿瘤一种新兴的治疗方法。
