窄頻中紅外線誘發肺腺癌細胞週期滯留之研究

Abstract

紅外光根據波長可以分為近紅外光（0.76-1.5 μm)、中紅外光（1.5-5.6 μm)以及遠紅外光（5.6-1000 μm)。目前紅外光對生物體產生的影響，只著重於近紅外光及遠紅外光部分，對於中紅外光的研究鮮少著墨。因此，本實驗利用波長3-5 微米的中紅外光來闡述中紅外光對於肺腺癌細胞造成的可能影響。從結果得知，我們發現波長3-5 微米的中紅外光可抑制肺腺癌細胞之生長、造成細胞型態較大且圓同時改變細胞骨架之微絲、微管及黏著斑蛋白之分布。利用即時聚合連鎖反應，我們發現中紅外光造成ATM, ATR, TP53, p21及GADD45基因表現量上升，並且造成Cyclin B及CDC2基因的表現量下降，以上基因的調控結果與G2/M 細胞週期滯留相關。除此之外，我們也發現CDC25C、Cyclin B1及磷酸化CDC2 (Thr-161)的蛋白質表現量下降，此蛋白質表現量下降之結果也與G2/M細胞週期滯留相關。同時，中紅外光可造成肺腺癌細胞核內形成53BP1及γ-H2AX foci，此現象與DNA傷害引起有關。因此我們推測G2/M細胞週期滯留可能是由DNA傷害所造成。研究中，可指出中紅外光是一具有潛力之肺腺癌治療方法。

Infrared radiation (IR) can be divided into near-infrared radiation (NIR, 0.76-1.5 μm), middle-infrared radiation (MIR, 1.5-5.6 μm) and far-infrared radiation (FIR, 5.6-1000 μm) according to the increasing wavelength. Although there are researches about NIR and FIR in cancer cells, the effects of MIR are still unclear. In this study, MIR in narrow bandwidth with wavelength from 3 to 5 μm was utilized to irradiate lung adenocarcinoma cells A549 for 48 h. We found that MIR exposure could inhibit the cell proliferation, result in enlarged and rounded cell shape, and alter the cellular distribution of F-actin, vinculin and microtubule. Using quantitative PCR, we found MIR promoted the expression levels of ATM, ATR, TP53, p21 and GADD45, but decreased the expression levels of Cyclin B and CDC2, inferring MIR might lead to G2/M arrest in A549 cells. Moreover, MIR also decreased the protein levels of CDC25C, Cyclin B1 and phosphorylation of CDC2 at Thr-161. In advanced, MIR exposure initiated the formation of 53BP1 and γ-H2AX nuclei foci implies that MIR might trigger G2M arrest by causing DNA breakage. Taken together, we revealed that MIR could inhibit A549 cell proliferation through G2/M cell cycle arrest. This study may provide useful information for lung cancer therapy.