Urbasic Ashlee S, Hynes Stacy, Somrak Amy, Contakos Stacey, Rahman Masmudur M, Liu Jia, MacNeill Amy L
Department of Pathobiology, University of Illinois, Urbana, IL 61802, USA.
Am J Vet Res. 2012 Aug;73(8):1252-61. doi: 10.2460/ajvr.73.8.1252.
To determine the oncolytic efficacy of an attenuated form of myxoma virus lacking the serp2 gene in canine tumor cells.
Primary cells were isolated from tumors that were surgically removed from dogs and from connective tissue obtained from the cadaver of a dog. Cells of various established cell lines from tumors and nontumorous tissues were obtained.
Experiments were performed with cells in monolayer culture. Cell cultures were inoculated with wild-type myxoma viruses or myxoma viruses lacking the serp2 gene, and measures of cytopathic effects, viral growth kinetics, and cell death and apoptosis were determined.
Myxoma viruses replicated in cells of many of the primary and established canine tumor cell lines. Canine tumor cells in which expression of activated protein kinase B was upregulated were more permissive to myxoma virus infection than were cells in which expression of activated protein kinase B was not upregulated. Myxoma viruses lacking the serp2 gene caused more cytopathic effects in canine tumor cells because of apoptosis than did wild-type myxoma viruses.
Results of the present study indicated myxoma viruses lacking the serp2 gene may be useful for treatment of cancer in dogs. Impact for Human Medicine-Results of the present study may be useful for development of novel oncolytic treatments for tumors in humans.
确定缺失serp2基因的减毒黏液瘤病毒在犬肿瘤细胞中的溶瘤效力。
原代细胞从手术切除的犬肿瘤以及从犬尸体获取的结缔组织中分离得到。还获取了来自肿瘤和非肿瘤组织的各种已建立细胞系的细胞。
实验在单层培养的细胞中进行。细胞培养物接种野生型黏液瘤病毒或缺失serp2基因的黏液瘤病毒，并测定细胞病变效应、病毒生长动力学以及细胞死亡和凋亡情况。
黏液瘤病毒在许多原代和已建立的犬肿瘤细胞系的细胞中复制。活化蛋白激酶B表达上调的犬肿瘤细胞比活化蛋白激酶B表达未上调的细胞对黏液瘤病毒感染更敏感。缺失serp2基因的黏液瘤病毒由于凋亡在犬肿瘤细胞中引起的细胞病变效应比野生型黏液瘤病毒更强。
本研究结果表明，缺失serp2基因的黏液瘤病毒可能对犬癌症治疗有用。对人类医学的影响——本研究结果可能有助于开发针对人类肿瘤的新型溶瘤治疗方法。
