J Cancer 2019; 10(4):1060-1069. doi:10.7150/jca.27418

Research Paper

AAV-Mig-6 Increase the Efficacy of TAE in VX2 Rabbit Model, Is Associated With JNK Mediated Autophagy

Zixuan Li1,2, Yulong Tian1,2, Lianyue Qu3, Jingsong Mao2,4, Hongshan Zhong1,2✉

1. Department of Interventional Radiology, The First Affiliated Hospital of China Medical University, Shenyang, China
2. Key Laboratory of Diagnostic Imaging and Interventional Radiology of Liaoning Province, Shenyang, China
3. Department of Pharmacy, The First Affiliated Hospital of China Medical University Shenyang, China
4. Department of Radiology, Xiang'an Hospital of Xiamen University, Xiamen, P. R. China

Abstract

The characterization of high recurrence rate of HCC after TAE provides insights into persistent issues surrounding the role of adjunct therapies administered with TAE. As a regulator of the HER family, Mig-6 is down-regulated in HCC and predicts the prognosis of HCC. In this study, we found up-regulation the expression of Mig-6 enhances autophagy in HCC cells. This function of Mig-6 is related to the activation of the JNK pathway. Next AAV-9 encoding Mitogen inducible gene 6 (Mig-6) was delivered into VX2 liver transplant tumor of rabbits by using hepatic artery catheter. Wild-type AAV is not associated with any human or animal disease and has very low immunogenicity. There are over 100 different AAV serotypes that vary in the amino acid sequence of their capsid protein. We also describe a novel combination therapy coupling AAV-Mig-6 and TAE in a rabbit model resulted in a growth rate decrease in tumor compared with TAE alone. Furthermore, we show that the changes of LC3b and p62, as well as the p-JNK were consistent with changes in vitro experiments. These results suggest that Mig-6 efficiently inhibits tumor progression in vivo. Our findings suggest that Mig-6 induced autophagy inhibition may become a necessary target for adjunct therapy in TAE.

Keywords: Mig-6, TAE, AAV, Autophagy, JNK

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How to cite this article:
Li Z, Tian Y, Qu L, Mao J, Zhong H. AAV-Mig-6 Increase the Efficacy of TAE in VX2 Rabbit Model, Is Associated With JNK Mediated Autophagy. J Cancer 2019; 10(4):1060-1069. doi:10.7150/jca.27418. Available from http://www.jcancer.org/v10p1060.htm