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. 2020 Nov 16:8:598997.
doi: 10.3389/fbioe.2020.598997. eCollection 2020.

Effects of Selenium Nanoparticles Combined With Radiotherapy on Lung Cancer Cells

Jingxia Tian  1 , Xiaoying Wei  2 , Weihua Zhang  1 , Aiguo Xu  3
Affiliations

Effects of Selenium Nanoparticles Combined With Radiotherapy on Lung Cancer Cells

Jingxia Tian et al. Front Bioeng Biotechnol. .

Abstract

Objective: To 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.

Methods: Nano-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.

Results: The 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.

Keywords: combination; lung cancer; radiotherapy; selenium nanoparticle; synergistic therapy.

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Figures

FIGURE 1
FIGURE 1
Characterization and identification of Nano-Se. (A,B) Observe the morphological size of nano-Se by TEM and draw a size histogram; (C) XRD analysis; (D) UV-Vis Spectroscopy analysis.
FIGURE 2
FIGURE 2
The effect of Nano-Se and its combination with radiotherapy on cell proliferation activity. (A,B) The effects of different concentrations of nano-Se (0 (Control), 0.25, 0.5, 1, 2, 5, 10, 15, and 20 μg/mL) on the proliferation of NSCLC cells A549 and NCI-H23; (C,D) After 1 μg/mL nano-Se pretreated NSCLC cells A549 and NCI-H23, the effects of different doses of radiation treatment (0 (Control), 2, 4, and 6 Gy) on cell proliferation activity. Compared with the Control group, **P < 0.01, ***P < 0.001; comparison between different concentrations of nano-Se treatment group, ###P < 0.001; comparison between different dose radiation treatment groups, &&P < 0.01, &&&P < 0.001.
FIGURE 3
FIGURE 3
The uptake of Nano-Se by NSCLC cells. (A–E) Nano-Au, different concentrations of nano-Se (0, 0.5, and 1 μg/mL) treated A549 cells, the cell absorption of nanoparticles.
FIGURE 4
FIGURE 4
The effects of Nano-Se combined with radiotherapy on cell migration. (A) The migration changes of A549 cells; (B) The migration changes of NCI-H23 cells. Compared with the Control group, *P < 0.05.
FIGURE 5
FIGURE 5
The effects of Nano-Se combined with radiotherapy on cell invasion. (A) Invasion of A549 cells; (B) Invasion of NCI-H23 cells. Compared with the Control group, *P < 0.05, **P < 0.01.
FIGURE 6
FIGURE 6
The effects of Nano-Se combined with radiotherapy on cell apoptosis. (A) Apoptosis of A549 cells; (B) Apoptosis of NCI-H23 cells. Compared with the Control group, *P < 0.05, **P < 0.01, ***P < 0.001.
FIGURE 7
FIGURE 7
The effects of Nano-Se combined with radiotherapy on the level of protein expression in cells. Compared with the Control group, *P < 0.05, **P < 0.01, ***P < 0.001.
FIGURE 8
FIGURE 8
Mechanism pathway diagram of nano-Se acting on NSCLC cells.
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