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Mol. Cells 2012; 34(2): 143-148

Published online August 31, 2012

https://doi.org/10.1007/s10059-012-2291-4

© The Korean Society for Molecular and Cellular Biology

A Proteoliposome Containing Apolipoprotein A-I Mutant (V156K) Enhances Rapid Tumor Regression Activity of Human Origin Oncolytic Adenovirus in Tumor-Bearing Zebrafish and Mice

Juyi Seo1,2, Chae-Ok Yun3, Oh-Joon Kwon3, Eun-Jin Choi4, Jae-Young Song4, Inho Choi1,2, and Kyung-Hyun Cho1,2,*

1School of Biotechnology, Yeungnam University, Gyeongsan 712-749, Korea, 2Research Institute of Protein Sensor, Yeungnam University, Gyeongsan 712-749, Korea, 3Department of Bioengineering, College of Engineering, Hanyang University, Seoul 133-791, Korea, 4Viral Disease Division, Animal, Plant and Fisheries Quarantine and Inspection Agency (QIA), Anyang 430-757, Korea,

Correspondence to : *Correspondence: chok@yu.ac.kr

Received: December 27, 2011; Revised: May 28, 2012; Accepted: May 31, 2012

Abstract

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. Immunohistochemi-cal 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.

Keywords apolipoprotein A-I, oncolytic adenovirus, proteoliposome, reconstituted high-density lipoproteins, zebrafish

Article

Research Article

Mol. Cells 2012; 34(2): 143-148

Published online August 31, 2012 https://doi.org/10.1007/s10059-012-2291-4

Copyright © The Korean Society for Molecular and Cellular Biology.

A Proteoliposome Containing Apolipoprotein A-I Mutant (V156K) Enhances Rapid Tumor Regression Activity of Human Origin Oncolytic Adenovirus in Tumor-Bearing Zebrafish and Mice

Juyi Seo1,2, Chae-Ok Yun3, Oh-Joon Kwon3, Eun-Jin Choi4, Jae-Young Song4, Inho Choi1,2, and Kyung-Hyun Cho1,2,*

1School of Biotechnology, Yeungnam University, Gyeongsan 712-749, Korea, 2Research Institute of Protein Sensor, Yeungnam University, Gyeongsan 712-749, Korea, 3Department of Bioengineering, College of Engineering, Hanyang University, Seoul 133-791, Korea, 4Viral Disease Division, Animal, Plant and Fisheries Quarantine and Inspection Agency (QIA), Anyang 430-757, Korea,

Correspondence to:*Correspondence: chok@yu.ac.kr

Received: December 27, 2011; Revised: May 28, 2012; Accepted: May 31, 2012

Abstract

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. Immunohistochemi-cal 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.

Keywords: apolipoprotein A-I, oncolytic adenovirus, proteoliposome, reconstituted high-density lipoproteins, zebrafish

Mol. Cells
Aug 31, 2022 Vol.45 No.8, pp. 513~602
COVER PICTURE
Cryo-EM structure of human porphyrin transporter ABCB6 (main figure) shows that binding of hemin (inset, magenta) in concert with two glutathione molecules (cyan) primes ABCB6 for high ATP turnover (Kim et al., pp. 575-587).

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