ID 276
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トクセイ エンセキガイセン ショウシャ ニヨル ガンサイボウ ノ ドウタイ ニ カンスル ケンキュウ
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The Dynamic Phase of Cancer Cells by the Low Temperature Narrow Wavelength Far Infrared Radiation
Hosokawa, Hiroyoshi Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry, The University of Tokushima
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Departmental Bulletin Paper
Far infrared ray (FIR) are known to have some effects on the human body, but little is known about the non-fever effects in normal thermal fields. We developed a CO_2 incubator and an animal raiser that is able to radiate low temperature narrow wavelength (limited) FIR at wavelength of 4 to 20μm with a peak wavelength 7 to 12μm, which had strong effects on living tissue, and we investigated the effects of this FIR on cancer cells. In in vitro analyses, analyses of cell proliferation and cell cycle were carried out using 5-bromo-2-deoxy-uridine (BrdU) incorporation and flowcytometry in three cancer cell lines: the human vulval epidermal cell line A431, the human tongue squamous cell carcinoma (SCC) line HSC3, and the human gingiva SCC line Sa3. In addition, from the viewpoint of the heat shock proteins (HSPs), especially the HSP70 protein, having cytoprotection for various stresses, Hsp70A gene expression was examined using real-time reverse transcription polymerase chain reaction. The effect of HSP70 protein on cell proliferation for limited FIR was analyzed by transfecting Hsp70A expression vector or by repressing Hsp70A and Hsp70C mRNA using gene silencing methods with siRNA. In in vivo analyses, we generated xenograft tumors of A431 and Sa3 cells and examined the changes of tumor volume, genetic alteration and histological observation. As a result, limited FIR suppressed cell proliferation of HSC3 and Sa3 cells, not A431 cells. The cell cycle of HSC3 cells was mainly delayed by limited FIR in the G2/M stage, while necrotic cells of Sa3 cells slightly increased by limited FIR. Moreover, the expression of Hsp70A gene and HSP70 protein was higher on A431 cells whose cell proliferation was not suppressed by limited FIR. On BrdU incorporation analysis under the condition in which HSP70 protein was repressed, BrdU incorporation of A431 cells was suppressed. In in vivo analyses, limited FIR suppressed both the growth of A431 tumor and Sa3 tumor. Tumor tissues of A431 in limited FIR group were encapsulated and matrix metalloproteinase (MMP)-1, -9, -10, -13 were significantly suppressed in the protein level. On the other hand, limited FIR induced the apoptosis in the Sa3 tumor. These findings in vitro suggest that limited FIR suppressed the proliferation of certain cancer cells, and the suppressive effect depended on expression level of HSP70 protein. These findings in vivo that limited FIR suppressed the tumor growth of A431 by inhibiting MMPs, and that of Sa3 by inducing apoptosis.
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