Tumor‑treating fields in combination with sorafenib restrain the proliferation of liver cancer <em>in vitro</em>

Jang,Yoonjung; Lee,Won Seok; Sai,Sei; Kim,Jeong Yub; Kim,Jong-Ki; Kim,Eun Ho

doi:10.3892/ol.2022.13458

Tumor‑treating fields in combination with sorafenib restrain the proliferation of liver cancer in vitro

Authors:
- Yoonjung Jang
- Won Seok Lee
- Sei Sai
- Jeong Yub Kim
- Jong-Ki Kim
- Eun Ho Kim
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Affiliations: Department of Biochemistry, School of Medicine, Daegu Catholic University, Daegu, North Gyeongsang 42471, Republic of Korea, Department of Basic Medical Sciences for Radiation Damage, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba 263‑8555, Japan, Division of Radiation Biomedical Research, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Republic of Korea, Department of Biomedical Engineering and Radiology, School of Medicine, Daegu Catholic University, Daegu, North Gyeongsang 42471, Republic of Korea
Published online on: August 11, 2022 https://doi.org/10.3892/ol.2022.13458
Article Number: 338

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Abstract

Liver cancer is a common malignancy worldwide, with a poor prognosis and a high recurrence rate despite the available treatment methodologies. Tumor‑treating fields (TTFields) have shown good preclinical and clinical results for improving the prognosis of patients with glioblastoma and malignant pleural mesothelioma. However, there is minimal evidence for the effect of TTFields on other cancer types. Thus, the present study aimed to investigate the therapeutic efficacy of TTFields in an in vitro model, and to further elucidate the underlying mechanisms. In the present study, two hepatocellular carcinoma (HCC) cell lines (Hep3B and HepG2) were treated with TTFields (intensity, 1.0 V/cm; frequency, 150 kHz) in order to determine the potential antitumor effects of this approach. TTFields significantly inhibited the proliferation and viability of HCC cell lines, as measured using Trypan blue and MTT assays, as well as colony formation in three‑dimensional cultures. The TTFields also significantly inhibited the migration and invasion of HCC cells in Transwell chamber and wound‑healing assays. Moreover, TTFields enhanced the production of reactive oxygen species in the cells and increased the proportion of apoptotic cells, as evidenced by increased caspase‑3 activity, as well as PARP cleavage in western blotting experiments. All of these effects were increased following the application of TTFields in combination with the multi‑kinase inhibitor sorafenib, which demonstrated a synergistic effect. Thus, to the best of our knowledge, these results demonstrate for the first time the potential of TTFields in improving the sensitivity of HCC cells to sorafenib, which may lay the foundation for future clinical trials for this combination treatment strategy.

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