Development of single nanometer-sized ultrafine oxygen bubbles to overcome the hypoxia-induced resistance to radiation therapy via the suppression of hypoxia-inducible factor‑1α.
Development of single nanometer-sized ultrafine oxygen bubbles to overcome the hypoxia-induced resistance to radiation therapy via the suppression of hypoxia-inducible factor‑1α.
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DOI：
10.3892/ijo.2018.4248
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发表时间：
2018-03
影响因子：
5.2
通讯作者：
Yamanouchi D
中科院分区：
文献类型：
--
作者：
Iijima M;Gombodorj N;Tachibana Y;Tachibana K;Yokobori T;Honma K;Nakano T;Asao T;Kuwahara R;Aoyama K;Yasuda H;Kelly M;Kuwano H;Yamanouchi D
放射治疗可能导致严重的副作用，包括放射抵抗力的发展。本研究的目的是验证使用氧气纳米气泡水通过抑制缺氧诱导因子1-α（HIF-1α）亚基来克服癌细胞系的辐射抗性。氧气纳米气泡水是使用一种新开发的方法来制造的，该方法使用PMPM-5设备在单纳米范围内产生纳米气泡。使用低温透射电子显微镜检查水中的氧纳米气泡的大小和浓度。纳米气泡的尺寸范围为2 - 3 nm，纳米气泡的浓度计算为2×1018个颗粒/ml。在体外常氧和缺氧条件下，在用或不用纳米气泡水和辐射处理的EBC-1肺癌和MDA-MB-231乳腺癌细胞中评价细胞活力和HIF-1α水平。与在用蒸馏水制成的培养基中生长的细胞相比，在含氧纳米气泡的培养基中生长的癌细胞表现出对缺氧诱导的HIF-1α表达的明显抑制。在低氧条件下，EBC-1和MDA-MB 231细胞显示出对辐射的抵抗力，与常氧细胞下培养的细胞相比。与使用2、6、10和14戈伊剂量的正常培养基相比，使用氧纳米泡培养基显著抑制了缺氧诱导的对辐射的抵抗。重要的是，在常氧条件下，使用纳米气泡培养基不会影响癌细胞系或非癌细胞系BEAS-2B的活力和辐射敏感性。这种新产生的单纳米范围的氧气纳米气泡水，没有任何添加剂，因此可能被证明是一种有前途的试剂，可用于通过抑制HIF-1α来克服缺氧诱导的癌细胞对辐射的抵抗。
Radiation therapy can result in severe side-effects, including the development of radiation resistance. The aim of this study was to validate the use of oxygen nanobubble water to overcome resistance to radiation in cancer cell lines via the suppression of the hypoxia-inducible factor 1-α (HIF-1α) subunit. Oxygen nanobubble water was created using a newly developed method to produce nanobubbles in the single-nanometer range with the ΣPM-5 device. The size and concentration of the oxygen nanobubbles in the water was examined using a cryo-transmission electron microscope. The nanobubble size was ranged from 2 to 3 nm, and the concentration of the nanobubbles was calculated at 2×1018 particles/ml. Cell viability and HIF-1α levels were evaluated in EBC-1 lung cancer and MDA-MB-231 breast cancer cells treated with or without the nanobubble water and radiation under normoxic and hypoxic conditions in vitro. The cancer cells grown in oxygen nanobubble-containing media exhibited a clear suppression of hypoxia-induced HIF-1α expression compared to the cells grown in media made with distilled water. Under hypoxic conditions, the EBC-1 and MDA-MB231 cells displayed resistance to radiation compared to the cells cultured under normoxic cells. The use of oxygen nanobubble medium significantly suppressed the hypoxia-induced resistance to radiation compared to the use of normal medium at 2, 6, 10 and 14 Gy doses. Importantly, the use of nanobubble media did not affect the viability and radiation sensitivity of the cancer cell lines, or the non-cancerous cell line, BEAS-2B, under normoxic conditions. This newly created single-nanometer range oxygen nanobubble water, without any additives, may thus prove to be a promising agent which may be used to overcome the hypoxia-induced resistance of cancer cells to radiation via the suppression of HIF-1α.
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