Radiofrequency hyperthermia-enhanced herpes simplex virus-thymidine kinase/ganciclovir direct intratumoral gene therapy of hepatocellular carcinoma.
Mo kle
Abstrè
OBJECTIVE
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).
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 < .05). Ultrasound imaging of treated animal xenografts showed smaller relative tumour volume in combination therapy group than those in three control groups (0.74 ± 0.19 vs. 1.79 ± 0.24, 3.14 ± 0.49 and 3.22 ± 0.52, p < .05). Optical imaging demonstrated significant decrease of bioluminescence signals of tumours in the combination therapy group, compared to those in three control groups (1.2 ± 0.1 vs. 1.9 ± 0.2% vs. 3.3 ± 0.6% vs. 3.5 ± 0.4%, p < .05). These imaging findings were correlated well with histologic confirmation.
CONCLUSIONS
RFH can enhance HSV-TK/GCV-mediated gene therapy of HepG2 cell line and mice human HCC xenografts, which may open new avenues for effective management of HCC using MR/RFH integrated interventional gene therapy.
