Tumor-Treating Fields Induce RAW264.7 Macrophage Activation Via NK-kappa B/MAPK Signaling Pathways
- Authors
- Park, Jeong-In; Song, Kyung-Hee; Jung, Seung-Youn; Ahn, Jiyeon; Hwang, Sang-Gu; Kim, Joon; Kim, Eun Ho; Song, Jie-Young
- Issue Date
- 9-Aug-2019
- Publisher
- SAGE PUBLICATIONS INC
- Keywords
- TTFs; cancer; immune; cytokine; MAPK; NF-kappa B
- Citation
- TECHNOLOGY IN CANCER RESEARCH & TREATMENT, v.18
- Indexed
- SCIE
SCOPUS
- Journal Title
- TECHNOLOGY IN CANCER RESEARCH & TREATMENT
- Volume
- 18
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/63542
- DOI
- 10.1177/1533033819868225
- ISSN
- 1533-0346
- Abstract
- Objective: Tumor-treating fields are currently used to successfully treat various cancers; however, the specific pathways associated with its efficacy remain unknown in the immune responses. Here, we evaluated tumor-treating fields-mediated initiation of the macrophage-specific immune response. Materials and Methods: We subjected RAW 264.7 mouse macrophages to clinically relevant levels of tumor-treating fields (0.9 V/cm, 150 kHz) and evaluated alterations in cytokine expression and release, as well as cell viability. Additionally, we investigated the status of immunomodulatory pathways to determine their roles in tumor-treating fields-mediated immune activation. Results and Discussion: Our results indicated that tumor-treating fields treatment at 0.9 V/cm decreased cell viability and increased cytokine messenger RNA/protein levels, as well as levels of nitric oxide and reactive oxygen species, relative to controls. The levels of tumor necrosis factor alpha, interleukin 1 beta, and interleukin 6 were markedly increased in tumor-treating fields-treated RAW 264.7 cells cocultured with 4T1 murine mammary carcinoma cells compared with those in 4T1 or RAW 264.7 cells with or without tumor-treating fields treatment. Moreover, the viability of 4T1 cells treated with the conditioned medium of tumor-treating fields-stimulated RAW 264.7 cells decreased, indicating that macrophage activation by tumor-treating fields effectively killed the tumor cells. Moreover, tumor-treating fields treatment activated the nuclear factor kappa B and mitogen-activated protein kinase pathways involved in immunomodulatory signaling. Conclusion: These results provide critical insights into the mechanisms through which tumor-treating fields affect macrophage-specific immune responses and the efficacy of this method for cancer treatment.
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Collections - Graduate School > Department of Life Sciences > 1. Journal Articles
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