Tumor-Treating Fields Induce RAW264.7 Macrophage Activation Via NK-?B/MAPK Signaling Pathways

Park, Jeong-In; Song, Kyung-Hee; Jung, Seung-Youn; Ahn, Jiyeon; Hwang, Sang-Gu; Kim, Joon; Kim, Eun Ho; Song, Jie-Young

Administration of TTFs did not cause cell death in RAW 264.7 cells; however, cell growth inhibition was clearly observed, suggesting that highly proliferating cancer cells are selectively targeted by TTFs therapy. Lipopolysaccharidetreated cells were morphologically changed from a roundshape to dendritic-like shape, and the number of cells was Figure 4 . Activation of RAW 264.7 cells via MAPK and NF-kB signaling pathways. A, RAW 264.7 cells were treated with TTFs (0.9 V/cm) or LPS (1 ng/mL) for 24 hours. Levels of the indicated proteins were determined with Western blotting, and GAPDH was used as the internal control. A representative result of 3 independent experiments is shown. B, Band intensities corresponding to the indicated proteins were quantified by densitometry using Image J software, normalized to the GAPDH, and expressed as the fold-change from each control. Data represent the mean (standard deviation) of triplicate samples. *P < .05 compared with the control group. LPS indicates lipopolysaccharide; MAPK, mitogen-activated protein kinase; NF-kB, nuclear factor-kB; TTFs, tumor-treating fields. decreased at the early stages but was subsequently recovered. Therefore, the effect of TTFs on various types of normal cells should be further investigated, and in vivo assays are also needed. Although this study cannot be extrapolated to in vivo conditions, it may provide a theoretical and experimental basis for immune responses specific to TTF treatments in the future.