A proteoliposome containing apolipoprotein A-I mutant (V156K) enhances rapid tumor regression activity of human origin oncolytic adenovirus in tumor-bearing zebrafish and mice

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• 作者：Juyi Seo (1) (2)
  Chae-Ok Yun (3)
  Oh-Joon Kwon (3)
  Eun-Jin Choi (4)
  Jae-Young Song (4)
  Inho Choi (1) (2)
  Kyung-Hyun Cho (1) (2)
  
• 关键词：apolipoprotein A–I ; oncolytic adenovirus ; proteoliposome ; reconstituted high ; density lipoproteins ; zebrafish
• 刊名：Molecules and Cells
• 出版年：2012
• 出版时间：August 2012
• 年：2012
• 卷：34
• 期：2
• 页码：143-148
• 全文大小：731KB
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• 作者单位：Juyi Seo (1) (2)
  Chae-Ok Yun (3)
  Oh-Joon Kwon (3)
  Eun-Jin Choi (4)
  Jae-Young Song (4)
  Inho Choi (1) (2)
  Kyung-Hyun Cho (1) (2)
  
  1. School of Biotechnology, Yeungnam University, Gyeongsan, 712-749, Korea
  2. Research Institute of Protein Sensor, Yeungnam University, Gyeongsan, 712-749, Korea
  3. Department of Bioengineering, College of Engineering, Hanyang University, Seoul, 133-791, Korea
  4. Viral Disease Division, Animal, Plant and Fisheries Quarantine and Inspection Agency (QIA), Anyang, 430-757, Korea
  
• ISSN：0219-1032

文摘

We recently reported that the efficiency of adenoviral gene delivery and virus stability are significantly enhanced when a proteoliposome (PL) containing apolipoprotein (apo) A–I is used in an animal model. In the current study, we tested tumor removal activity of oncolytic adenovirus (Ad) using PL-containing wildtype (WT) or V156K. Oncolytic Ad with or without PL was injected into tumors of zebrafish and nude mice as a Hep3B tumor xenograft model. The V156K-PL-Ad-injected zebrafish, group showed the lowest tumor tissue volume and nucleic acids in the tumor area, whereas injection of Ad alone did not result in adequate removal of tumor activity. Reactive oxygen species (ROS) contents increased two-fold in tumor-bearing zebrafish; however, the V156K-PL-Ad injected group showed a 40% decrease in ROS levels compared to that in normal zebrafish. After reducing the tumor volume with the V156K-PL-Ad injection, the swimming pattern of the zebrafish changed to be more active and energetic. The oncolytic effect of PL-Ad containing either V156K or WT was about two-fold more enhanced in mice than that of Ad alone 34 days after the injection. Immunohistochemical analysis revealed that the PL-Ad-injected groups showed enhanced efficiency of viral delivery with elevated Ad-E1A staining and a diminished number of proliferating tumor cells. Thus, the antitumor effect of oncolytic Ad was strongly enhanced by a PL-containing apoA-I and its mutant (V156K) without causing side effects in mice and zebrafish models.