Lee Che-Hsin, Nishikawa Tomoyuki, Kaneda Yasufumi
Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan.
Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan.
Oncotarget. 2017 May 23;8(21):35048-35060. doi: 10.18632/oncotarget.17037.
Salmonella can target to tumor microenvironments after systemic treatment. The hemagglutinating virus of Japan-envelope (HVJ-E) induced apoptosis in tumor cells without toxicity in normal cells. Current HVJ-E therapeutic strategies, aimed at using HVJ-E for intratumor treatment, have shown great promise in animal models but have achieved only limited systemic treatment. The purpose of this study was to investigate the modulation of the anti-tumor efficiency of HVJ-E by coating the particles with poly (allylamine hydrochloride) (PAH), designated as P-HVJ-E. Treatment with P-HVJ-E resulted in decreased hemagglutinating activity and maintained tumor cell-selective apoptosis and anti-tumor immunity. The use of Salmonella as a coating for P-HVJ-E (PHS) enhanced the antitumor activity and maintained the tumor-targeting activity. Treatment with PHS resulted in delayed tumor growth in tumor-bearing mice. Furthermore, a Western blot assay of the tumors revealed that HVJ-E targeted to the tumor after systemic treatment with PHS. These results indicate that Salmonella coating viral particles may provide a new approach for tumor therapy.
全身治疗后，沙门氏菌可靶向肿瘤微环境。日本血凝病毒包膜（HVJ-E）可诱导肿瘤细胞凋亡，而对正常细胞无毒性。目前的HVJ-E治疗策略旨在将HVJ-E用于肿瘤内治疗，在动物模型中已显示出巨大潜力，但全身治疗效果有限。本研究的目的是通过用聚（烯丙胺盐酸盐）（PAH）包被颗粒（命名为P-HVJ-E）来研究对HVJ-E抗肿瘤效率的调节作用。用P-HVJ-E处理导致血凝活性降低，并维持肿瘤细胞选择性凋亡和抗肿瘤免疫。使用沙门氏菌作为P-HVJ-E（PHS）的包被增强了抗肿瘤活性并维持了肿瘤靶向活性。用PHS处理导致荷瘤小鼠肿瘤生长延迟。此外，对肿瘤进行的蛋白质印迹分析表明，用PHS全身治疗后，HVJ-E靶向肿瘤。这些结果表明，沙门氏菌包被病毒颗粒可能为肿瘤治疗提供一种新方法。
