Response of human cancer cells to simultaneous treatment with sorafenib and radiofrequency current

Hernández‑Bule,María Luisa; Martínez,María Antonia; Trillo,María Ángeles; Martínez,Lidia; Toledano‑Macías,Elena; Úbeda,Alejandro

doi:10.3892/ol.2021.13068

Response of human cancer cells to simultaneous treatment with sorafenib and radiofrequency current

Authors:
- María Luisa Hernández‑Bule
- María Antonia Martínez
- María Ángeles Trillo
- Lidia Martínez
- Elena Toledano‑Macías
- Alejandro Úbeda
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Affiliations: Bioelectromagnetism‑Research Service, Ramón y Cajal University Hospital, IRYCIS, Madrid 28034, Spain
Published online on: September 23, 2021 https://doi.org/10.3892/ol.2021.13068
Article Number: 807
Copyright: © Hernández‑Bule et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Due to their alleged analgesic, anti‑inflammatory and tissue regenerative effects, capacitive‑resistive electrothermal therapy (CRET), which is based on non‑invasive exposure to radiofrequency (RF) currents, is often applied to chemotherapeutically treated patients with cancer. Our previous studies have demonstrated that subthermal CRET currents can elicit a number of cell responses, including anti‑proliferative effects, in the human liver cancer cell line HepG2. Such effects involve significant changes in the regulation of proteins involved in MAPK signaling pathways, which are also implicated in the cancer cell response to standard anticancer drugs such as sorafenib. This overlap in response pathways may lead to competitive, neutralizing or blocking interactions between the electrical and chemical treatments, thus raising questions on the advisability of CRET treatment for their analgesic, anti‑inflammatory or other purposes in patients undergoing chemotherapy. The present study analyzed the effects of simultaneous treatment with sorafenib and 448‑kHz, subthermal CRET current on the proliferation and viability of HepG2 cell cultures. Cell viability was assessed through Trypan blue or XTT assays, while flow cytometry was applied for cell cycle and apoptosis analysis. The expression of proteins involved in cell proliferation were assessed by immunoblotting and immunofluorescence. The results revealed no evidence to suggest that the electrical treatment counteracted or neutralized the cellular response to sorafenib at the different conditions evaluated. Furthermore, at the standard pharmacological sorafenib concentration, 5 µM, the combined treatment elicited an anti‑proliferative response significantly stronger than that induced by each of the treatments when applied separately in HepG2 cells. These data do not support the hypothesis that CRET exposure may inhibit or diminish the effects of a chemotherapeutic drug used in cancer treatment, and highlights the requirement for further investigation into the cell response to the combined action of electrical and chemical treatments.

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