Oncotarget

Research Papers:

Radiofrequency hyperthermia promotes the therapeutic effects on chemotherapeutic-resistant breast cancer when combined with heat shock protein promoter-controlled HSV-TK gene therapy: Toward imaging-guided interventional gene therapy

Jingfeng Luo, Xiaotian Wu, Fei Zhou, Yurong Zhou, Tongchun Huang, Fei Liu, Guocan Han, Luming Chen, Weixian Bai, Xia Wu, Jihong Sun and Xiaoming Yang _

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Oncotarget. 2016; 7:65042-65051. https://doi.org/10.18632/oncotarget.11346

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Abstract

Jingfeng Luo1, Xiaotian Wu1, Fei Zhou1, Yurong Zhou1, Tongchun Huang1, Fei Liu1, Guocan Han1, Luming Chen1, Weixian Bai1, Xia Wu1, Jihong Sun1, Xiaoming Yang1,2

1Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China

2Image-Guided Bio-Molecular Intervention Research, Department of Radiology, University of Washington School of Medicine, Seattle, Washington, USA

Correspondence to:

Xiaoming Yang, email: xmyang@uw.edu

Jihong Sun, email: braversun@sina.com

Keywords: radiofrequency hyperthermia, heat shock protein promoter, HSV-TK, gene therapy, drug resistance

Received: April 07, 2016     Accepted: August 10, 2016     Published: August 17, 2016

ABSTRACT

Objective: Gene therapy is a frontier in modern medicine. In the present study, we explored a new technique for the effective treatment of multidrug-resistant (MDR) breast cancer by combining fully the advantages of multidisciplinary fields, including image-guided minimally invasive interventional oncology, radiofrequency technology, and direct intratumoral gene therapy.

Results: Combination treatment with PHSP-TK plus RFH resulted in significantly higher TK gene transfection/expression, as well as a lower cell proliferation rate and a higher cell apoptosis index, than those of control groups. In vivo validation experiments with MRI confirmed that combination therapy resulted in a significant reduction of relative tumor volume compared with those of control animals, which was supported by the results of histologic and apoptosis analyses.

Materials and methods: The heat shock protein promoter (PHSP) was used to precisely control the overexpression of thymidine kinase (TK) (PHSP-TK). Serial in vitro experiments were performed to confirm whether radiofrequency hyperthermia (RFH) could enhance PHSP-TK transfection and expression in a MDR breast cancer cell line (MCF7/Adr). Serial in vivo experiments were then carried out to validate the feasibility of the new technique, termed interventional RFH-enhanced direct intratumoral PHSP-TK gene therapy. The therapeutic effect of combination therapy was evaluated by MRI and confirmed by subsequent laboratory correlation.

Conclusions: This study has established “proof-of-principle” of a new technique, interventional RFH-enhanced local gene therapy for MDR breast cancer, which may open new avenues for the effective management of MDR breast cancers via the simultaneous integration of interventional oncology, RF technology, and direct intratumoral gene therapy.


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