ヒト癌細胞株における遠赤外線効果の遺伝子発現解析
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概要
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Far-infrared radiation (FIR) is electromagnetic radiation with wavelengths between 4 and 1000μm. The available evidence indicates that in vivo and in vitro irradiation by FIR has many biological effects, but how it affects cells is not well understood. Our previous studies using A431, HSC3 and Sa3 cells suggested that FIR inhibited cell proliferation by delaying the cell cycle in the G_2/M stage in HSC3 cells, while necrotic cells of Sa3 cells slightly increased. In addition, the basal expression of HSP70 was higher in FIR-insensitive A431 cells than in FIR-sensitive HSC3 and Sa3 cells, suggesting that the suppressive effect of FIR depends on HSP70 expression level in vitro. During in vivo analysis, FIR inhibited tumor growth in the A431 tumorigenesis model mouse by inhibiting the expression of matrix metalloprotease-1, 9, 10, and 13. In this study, we used a tissue culture incubator that can continuously irradiate cells with FIR, and we used it to examine the effects of a body temperature range of FIR on five human cancer cell lines, namely A431 (vulva), A549 (lung), HSC3 (tongue), MCF7 (breast), and Sa3 (gingiva). We found that FIR inhibits cell proliferation and induces cell hypertrophy in A549, HSC3, and Sa3 cells. In contrast, FIR did not inhibit cell proliferation, or cause cell hypertrophy in A431 or MCF7 cells. Also, FIR did not cause apoptosis in any of the five cell lines tested. cDNA microarray analysis revealed that FIR suppressed the expression of cell proliferation-related and stress-responsive genes in FIR-sensitive cell lines (A549, HSC3, and Sa3). Additionally, ATF3, in particular, was identified as a key mediator of the FIR effect. Overexpression of ATF3 inhibited the cell proliferation of A431, HSC3, and Sa3 cells, and knockdown of ATF3 mRNA using an antisense oligonucleotide suppressed FIR-induced growth arrest in HSC3 cells. In addition, the basal expression level of HSP70A mRNA was higher in A431 and MCF7 cells than in the FIR-sensitive A549, HSC3 and Sa3 cells. Also, HSP70A showed a high correlation with the growth rate out of the 35 HSP genes on the microarray. These results indicate that the body temperature range of FIR radiation suppresses the proliferation of A549, HSC3, and Sa3 cells, and it appears that ATF3 and HSP70 play important roles in this effect.
- 徳島大学の論文