Int J Biol Sci 2019; 15(2):386-394. doi:10.7150/ijbs.28356
Synergistic anti-tumor effects of arsenic trioxide and blue LED irradiation on human osteosarcoma
1. Department of Orthopedics, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
2. 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.
3. Department of Pharmacy, The First Affiliated Hospital of Harbin Medical University, Harbin 150086, China.
4. Department of Pharmacology, College of Pharmacy, Mudanjiang Medical University, Mudanjiang 157011, China.
5. Central Laboratory of Scientific Research, Bashkir State Medical University, Ufa 450008, Russia.
*Equal contributors to this work
Feng C, Gong R, Zheng Q, Yan G, He M, Lei H, Li X, Zhang L, Xu Z, Liu S, Yu M, Ma T, Gao M, Bamba D, Idiiatullina E, Zagidullin N, Pavlov V, Xu C, Yuan Y, Yang L. Synergistic anti-tumor effects of arsenic trioxide and blue LED irradiation on human osteosarcoma. Int J Biol Sci 2019; 15(2):386-394. doi:10.7150/ijbs.28356. Available from http://www.ijbs.com/v15p0386.htm
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.
Keywords: Osteosarcoma (OS), Blue LED irradiation, Arsenic trioxide (ATO), DNA damage, p53