Orthotopic hepatic cancer: radiofrequency hyperthermia-enhanced intratumoral herpes simplex virus-thymidine kinase gene therapy

// Fu Xiong 1, 2, * , Feng Zhang 2, * , Yin Jin 2 , Qiaoyou Weng 2 , Jingjing Song 2 , Guofeng Zhou 1 , David Shin 2 , Chuansheng Zheng 1 and Xiaoming Yang 2 1 Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province 430022, China 2 Image-Guided Bio-Molecular Intervention Research and Section of Vascular & Interventional Radiology, Department of Radiology, University of Washington School of Medicine, Seattle, WA 98109, USA * These authors have contributed equally to this work Correspondence to: Xiaoming Yang, email: xmyang@uw.edu Chuansheng Zheng, email: hqzcsxh@sina.com Keywords: radiofrequency hyperthermia; gene therapy; hepatocellular carcinoma; molecular imaging Received: July 04, 2017 Accepted: September 08, 2017 Epub: December 22, 2017 Published: March 06, 2018 ABSTRACT Purpose: To validate the feasibility of using interventional radiofrequency hyperthermia(RFH) to enhance herpes simplex virus-thymidine kinase (HSV-TK)/ganciclovir (GCV) gene therapy of rat orthotopic hepatic cancer. Material and Methods : Rat hepatocellular carcinoma cells (MCA-RH-7777) were transduced with lentivirus/luciferase gene for optical imaging. In-vitro experiments with the luciferase cells and in-vivo experiments on rats with orthotopic hepatic tumors were divided into four treatment groups: (i) HSV-TK/GCV-mediated gene therapy combined with RFH; (ii) gene therapy alone; (iii) RFH alone; and (iv) phosphate buffered saline (PBS). Cell viability was evaluated by MTS assay and confocal microscopy, and HSV-TK gene expression in cells and tumors was quantified by western blotting. Bioluminescent optical imaging and ultrasound imaging were used to monitor and compare the photon signal and tumor size changes among different treatment groups overtime, respectively. The imaging findings were correlated with histology. Results: For in-vitro experiments, the combination therapy group (gene therapy + RFH) demonstrated the lowest cell proliferation by MTS assay, compared to the gene therapy alone, RFH alone, and PBS (26.1±3.2% vs 50.4±4.6% vs 82.9±6.3% vs 100%, p