Abstract
ObjectiveTo investigate the effects of selenium nanoparticles (nano-Se) combined with radiotherapy on the proliferation, migration, invasion, and apoptosis of non-small cell lung cancer (NSCLC) A549 and NCI-H23 cells.MethodsNano-Se was synthesized and characterized by transmission electron microscope (TEM), X-ray diffractometer, and Ultraviolet-visible (UV)-Vis Spectroscopy, separately. The uptake of nano-Se by lung cancer cells was detected by flow cytometry. Cell counting kit-8 (CCK-8) method was used to detect the antiproliferative activity of nano-Se combined with radiotherapy. Wound healing tests and transwell assay were used to detect the migration and invasion ability of the cells. Annexin V-fluorescein isothiocyanate (FITC)/Propidium iodide (PI) staining by flow cytometry was used to detect apoptosis. The expression of Cyclin D1 (CCND1), c-Myc, matrix metalloproteinase 2 (MMP2), MMP9, cleaved Caspase-3, and cleaved Caspase-9 were detected by Western blot.ResultsThe average diameter of nano-Se was 24.39 nm and the wavelength of nano-Se increased with the increase of radiation dose under UV-Vis Spectroscopy. The uptake of nano-Se in lung cancer cells was increased with the increase of nano-Se concentration. The nano-Se combined with radiotherapy decreased the proliferation activity of NSCLC cell lines A549 and NCI-H23 in a dose-dependent manner (all P < 0.05). Compared with the Control group, nano-Se combined with radiotherapy could significantly inhibit the migration and invasion of lung cancer cells (all P < 0.05), and the effects of the combination of nano-Se and radiotherapy was better than that of a single application (all P < 0.05). Furthermore, nano-Se combined with radiotherapy could induce apoptosis of lung cancer cells (P < 0.05) and nano-Se combined with radiotherapy could significantly inhibit the expression of proliferation-related proteins CCND1, c-Myc, invasion and migration-related proteins MMP2 and MMP9, but conversely promoted the expression of apoptosis-related proteins cleaved caspase-3 and cleaved caspase-9. Conclusion: This study found that nano-Se combined with radiotherapy plays an anti-cancer role in lung cancer cells by inhibiting cell proliferation, migration, and invasion, as well as inducing apoptosis, suggesting that nano-Se may be used as a radiosensitizer in the clinical treatment of lung cancer, but further research is still needed.
Highlights
Lung cancer is one of the major cancers in the world
Cell Counting Kit-8 (CCK-8) kit was purchased from Dojindo Co., Ltd., Japan, and Annexin V-fluorescein isothiocyanate (FITC)/Propidium iodide (PI) apoptosis kit was purchased from Sigma-Aldrich, United States
Based on the biological functions of nano-Se combined with radiotherapy on lung cancer cells, this study explored the mechanism, focusing on detecting the expression of several proteins related to cancer cell proliferation, invasion, metastasis, and apoptosis
Summary
Lung cancer is one of the major cancers in the world. Among different types of lung cancer, non-small cell lung cancer (NSCLC) accounts for approximately 85% of the incidence (Duma et al, 2019), 60% of which are diagnosed as advanced, chemotherapy and radiotherapy are the standard treatment of advanced NSCLC (Herbst et al, 2018). Radiotherapy and chemotherapy have become a recognized tumor treatment model. Compared with radiotherapy alone and chemotherapy or sequential therapy, combined therapy has a better effect on the continuous control of local tumors and the improvement of the cure rate (Pirker, 2020). As an antitumor drug and an essential trace element, selenium has an effective dose approximate to the toxicity level, which greatly limits its usage in clinical treatments (Bhattacharjee et al, 2014). Given the rare research on the effect of NanoSe on the function of lung cancer cells, this study intends to treat lung cancer cells through the combination of Nano-Se and radiotherapy to observe the changes in cell proliferation, invasion and migration ability, and the impacts of the above treatments on cell apoptosis, to provide new anti-cancer drugs for the clinical treatment of lung cancer
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