Department of Pharmacy, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China; and Department of Pharmacology, College of Pharmacy, Harbin Medical University, Harbin 150081, China.
Department of Pharmacy, The First Affiliated Hospital of Harbin Medical University, Harbin 150086, China.
Int J Biol Sci. 2019 Jan 1;15(2):386-394. doi: 10.7150/ijbs.28356. eCollection 2019.
Arsenic trioxide (ATO) has been well recognized as an anti-tumor agent for various human cancers. Recently, the blue light emitting diodes (LEDs)-based therapy has also been demonstrated to be potential therapeutic strategies for several cancers. However, the combination effects of ATO and blue LED on tumor suppression are still unclear. In this study, we determined whether combination of ATO and blue LED irradiation at 470 nm in wavelength exhibited superior anti-tumor activity in human osteosarcoma (OS). We observed that combination treatments of ATO and blue LED much more significantly decreased the percentages of proliferative cells, and increased apoptotic rate compared with any single treatments in U-2 OS cells. Furthermore, we found suppression of cell migration and invasion were much more pronounced in ATO plus blue LED treated group than single treated groups. Moreover, reactive oxygen species (ROS) assay and immunostaining of γ-H2A.X and p53 indicated that the combined treatments resulted in further markedly increases in ROS accumulation, DNA damage and p53 activity. Taken together, our study demonstrated synergistical anti-tumor effects of combined treatments of ATO and blue LED on human OS cells, which were associated with an increased ROS accumulation, DNA damaged mediated p53 activation.
三氧化二砷（ATO）已被广泛认可为治疗各种人类癌症的抗肿瘤药物。最近，基于蓝光发光二极管（LED）的治疗方法也被证明是几种癌症的潜在治疗策略。然而，ATO 和蓝色 LED 联合对肿瘤抑制的协同作用仍不清楚。在这项研究中，我们确定了波长为 470nm 的 ATO 和蓝色 LED 照射联合治疗是否在人骨肉瘤（OS）中表现出优越的抗肿瘤活性。我们观察到，与任何单一治疗相比，ATO 和蓝色 LED 的联合治疗更显著地降低了 U-2 OS 细胞中增殖细胞的比例，并增加了细胞凋亡率。此外，我们发现 ATO 加蓝色 LED 处理组的细胞迁移和侵袭抑制作用明显强于单一处理组。此外，活性氧（ROS）测定和 γ-H2A.X 和 p53 的免疫染色表明，联合处理导致 ROS 积累、DNA 损伤和 p53 活性进一步显著增加。总之，我们的研究表明，ATO 和蓝色 LED 的联合治疗对人骨肉瘤细胞具有协同的抗肿瘤作用，这与 ROS 积累增加、DNA 损伤介导的 p53 激活有关。
