Radiofrequency hyperthermia-enhanced herpes simplex virus-thymidine kinase/ganciclovir direct intratumoral gene therapy of hepatocellular carcinoma

Abstract

Purpose: To determine the feasibility of using radiofrequency hyperthermia (RFH) and to enhance the therapeutic effect of herpes simplex virus-thymidine kinase/ganciclovir (HSV-TK/GCV) for the treatment of hepatocellular carcinoma (HCC). Materials and methods: Human HCC cells (HepG2) were first transfected with lentivirus/luciferase. For both in vitro confirmation and in vivo validation, luciferase-labeled HCC cells and HCC tumour xenografts on mice received different treatments: (i) combination therapy of intratumoral HSV-TK/GCV-mediated gene therapy plus magnetic resonance imaging heating guidewire (MRIHG)-mediated RFH; (ii) gene therapy only; (iii) RFH only; and (iv) phosphate-buffered saline (PBS) as control. Cell proliferation was quantified. Tumour changes were monitored by ultrasound imaging and bioluminescence optical imaging before and at days 7 and 14 after treatments, which were correlated with subsequent histology. Results:In vitro, the lowest cell proliferation was seen in the combination therapy group compared with control groups (29 ± 6% vs. 56 ± 9%, 93 ± 4%, and 100 ± 5%, p