The combined treatment of 150 kHz tumor treating fields (TTFields) and sorafenib inhibits hepatocellular carcinoma in vitro and in vivo.

Abstract

e15653 Background: Hepatocellular carcinoma (HCC) is the third cause of cancer related mortality and the primary cause of cancer death. Tumor Treating Fields (TTFields) therapy is an effective anti-neoplastic treatment modality delivered via noninvasive application of low intensity, intermediate frequency, alternating electric fields. Sorafenib, an oral multikinase inhibitor is approved for patients with advanced HCC, yet its survival benefit is still limited. In this work we explored the potential of the use of TTFields alone and in combination with Sorafenib as a treatment for HCC. Methods: HepG2 and Huh-7D12 cells were treated with various TTFields frequencies for 72 hours using the inovitro system. Efficacy of the combined treatment of TTFields and Sorafenib (36-3000 nM) was tested by applying TTFields at the optimal frequency together with various drug concentrations. Cell counts, induction of apoptosis, cell cycle and clonogenic potential were determined. TTFields (1.2 V/cm) and Sorafenib (10 mg/kg) were applied for 6 days to rats injected to the liver with N1S1 HCC cells. Tumor growth was followed using MRI. Results: The optimal TTFields frequency was 150 kHz for both cell lines. TTFields application (1.0 - 1.7 V/cm, 72 hours) at 150 kHz led to 36-40% reduction in cell counts and to additional reduction of over 70% in the clonogenic potential. The combined treatment of TTFields and Sorafenib led to a significant reduction in the number of cells (p < 0.001) as compared to each treatment alone. The averaged tumor volume fold increase of the combination treatment group was significantly lower than the one observed in the: control group, the TTFields group and the Sorafenib group. Conclusions: The results presented in this work demonstrate that TTFields can be an effective treatment against HCC cells and that the combination with Sorafenib may further enhance treatment efficacy.