Department of Dentistry, Universidade Estadual de Montes Claros, Montes Claros, Minas Gerais, Brazil.
Hospital Dilson Godinho, Montes Claros, Minas Gerais, Brazil.
Pathol Oncol Res. 2020 Jan;26(1):433-442. doi: 10.1007/s12253-018-0517-2. Epub 2018 Nov 8.
Radiation Therapy (RT) is a treatment option for a large number of neoplasias. However, the effect of RT on the level of hypoxia markers is poorly understood. The present study aimed to investigate the effect of RT on the levels of hypoxic markers in Oral squamous cell carcinoma (OSCC). Evaluation of HIF-1α and miR-210 levels in OSCC was performed. Then a proteomic analysis was performed to identify candidate hypoxic targets of RT. To validate proteomic studies, the effect of RT on HIF-1α, miR-210, PDH-A and LDH-A levels under hypoxia was assessed by qRT-PCR. The impact of RT in hypoxia markers was evaluated in patients to confirm in vitro results. An increase in the HIF-1α levels was observed in OSCC. RT reduced OSCC cell proliferation and migration. Interestingly, hypoxia could revert the effect of radiation on OSCC phenotype. However, proteomics analyses suggested that LDH is one of the critical targets of RT even in hypoxia. Moreover, RT decreased HIF-1α, miR-210, and LDH even in hypoxia. The current study demonstrated that hypoxia could revert the effects of RT in the OSCC context. However, RT reduces the levels HIF-1α, miR-210 and LDH in vivo and in vitro. The consequences of RT in blood should be carefully investigated.
放射治疗（RT）是许多肿瘤的治疗选择。然而，RT 对缺氧标志物水平的影响知之甚少。本研究旨在探讨 RT 对口腔鳞状细胞癌（OSCC）中缺氧标志物水平的影响。评估了 OSCC 中 HIF-1α 和 miR-210 的水平。然后进行蛋白质组学分析以确定 RT 的候选缺氧靶标。为了验证蛋白质组学研究，通过 qRT-PCR 评估了 RT 在缺氧条件下对 HIF-1α、miR-210、PDH-A 和 LDH-A 水平的影响。为了在患者中确认体外结果，评估了 RT 对缺氧标志物的影响。在 OSCC 中观察到 HIF-1α 水平增加。RT 降低了 OSCC 细胞的增殖和迁移。有趣的是，缺氧可以逆转 RT 对 OSCC 表型的影响。然而，蛋白质组学分析表明，即使在缺氧条件下，LDH 也是 RT 的关键靶标之一。此外，RT 降低了 HIF-1α、miR-210 和 LDH，即使在缺氧条件下也是如此。本研究表明，在 OSCC 环境中，缺氧可以逆转 RT 的作用。然而，RT 降低了体内和体外 HIF-1α、miR-210 和 LDH 的水平。应仔细研究 RT 在血液中的后果。
