Osteosarcoma (OS) is the most frequently diagnosed malignant bone tumor, its incidence rates largely peak in adolescence and elderly with a bimodal distribution by age [[1], [2], [3]]. Currently, the prognosis of OS patients with metastatic diseases is still substantially worse even if the survival rate of OS patients with localized has reached approximately 70%–80% using traditional therapeutic approaches [1,4]. The characteristic of poor prognosis and easy recurrence make it critical to need a new non-invasive prognostic treatment to improve survival rates of OS patients in clinically. Particularly, limb salvage and postoperative quality of life are the most critical problems in OS treatment at present [5,6]. It is essential to research new therapy modalities to maintain the clinical treatment of OS patients.

Recently, photobiomodulation (PBM) therapy has been widely reported for various aspects such as anti-inflammatory and skin aging [7,8], wound healing [9], hair growth [10], circadian rhythm [11], anticancer therapies [12], and is currently gained considerable attention in the area of biomedical research. Light-emitting diodes (LEDs) has been applied in PBMT widely due to its lower cost, safety of device, variability of wavelengths and wearability [13]. Accumulated evidences suggested that blue light LED PBM therapy played a crucial role in suppressing cancer cell proliferation, and even had an efficient therapeutic effect in cancer clinical treatment. Oh et al. (2015, 2016, 2017) repeatedly discovered that blue light PBM played an anti-tumor role in various types of cancer cells via inducing apoptosis and autophagy, such as melanoma cells, B-cell lymphoma cells, fibrosarcoma cells and colon cancer [[14], [15], [16]]. Sparsa et al. (2010) had used 450 nm blue LED for melanoma clinical treatment. Results revealed that blue light significantly suppressed the metastasis and growth of melanoma in patients, which is related with necrosis caused by massive Reactive oxygen species (ROS) production [17]. Meanwhile, Kleinpening et al. (2010) also proved that blue light scarcely cause photoaging or DNA damage in a accumulative dose of 100 J/cm2 at 420 nm blue light, so it is safe to apply in clinical treatment of different cancer within a certain dose range [18].

Cell apoptosis, also known as programmed cell death, occupies a core position in anti-cancer treatment processes. Apoptosis is a tightly regulated form of cell death, a wide variety of stimuli such as oxidative stress, hypoxia, radiation, viral infections, DNA damage and oncogene activation, cause permeabilization of the outer mitochondrial membrane [[19], [20], [21]]. Later, apoptosis-related proteins including cytochrome c were released in response to variations in mitochondrial membrane potential (MMP), which then activated caspase 9 and caspase 3 to cause DNA fragmentation and cell apoptosis [22].

Currently, substantial researches revealed that blue LED irradiation repressed different cancer cells proliferation and promoted apoptosis by increasing ROS level, activating apoptosis-related proteins such as Caspase 3/8 [12]. Also, high doses of blue light or combined effects with drugs have been proven to effectively inhibit the proliferation of OS by inducing apoptosis [23]. Meanwhile, He et al. (2021) have already discovered that large doses (180, 360, 720 J/cm2) of blue LED PBM showed anti-tumor effects on human OS U-2OS by inducing ROS production, cell apoptosis and autophagy pathways [24].

Therefore, to further explore the impact of blue light on OS, we used different blue light parameters (Table 1) to irradiate human OS MG63 cells. Blue light PBM-mediated toxicity involves multiple mechanisms, especially the production of excessive ROS and loss of MMP. Increasing evidence suggested that ROS levels increased significantly in different cancer cells, such as B-cell lymphoma cells [25], colorectal cancer cells [26], Leukemia cells [27] and synovial sarcoma cells [28]. Hence, in this experiment, we preliminarily determined the cytotoxic of 460 nm blue light PBM in human OS MG63 cells, and evaluated the impact of blue light PBM on cell migration and ROS level, in line with the results of morphological and biochemical changes in OS MG63 cells, we further analyzed the molecular mechanisms and related biological pathways of blue light PBM in OS cells.