Anti‐proliferative and metastasis‐inhibiting effect of carbon ions on non‐small cell lung adenocarcinoma A549 cells

Abstract

Objective Carbon ions suppress the effect of glutathione peroxidase 4 (GPX4) on the proliferation and metastasis of lung adenocarcinoma A549 cells. Methods The clonogenic formation ability of A549 cells was calculated with different ray doses of radiation. Cell proliferation, cycle, and apoptosis of A549 cells after different ray irradiation were detected by cck8 and flow cytometry. The transwell assay was used to detect the cell migration and invasion after different rays of radiation to A549 cells. The GPX4 matrix metalloproteinase 2 and E-cadherin expression levels were assessed by immunofluorescence and western blot. Results At the dose of 4 Gy, A549 cell viability was 22.95 ± 5.00% and 55.52 ± 3.26% when treated with carbon ions and X-rays, respectively. The distribution of A549 cells arrested in the G2 phase by carbon ion irradiation was positively correlated with radiation dose, with a most significant increase at 4 Gy irradiation (t = 4.303, p < 0.05). The results of apoptosis after irradiation showed were no significant differences in apoptosis at 1 and 2 Gy of X-ray compared with 0 Gy, and 4 Gy irradiation significantly induced apoptosis in A549 cells (t = 30.520, p < 0.05). The apoptotic rate of carbon ion-irradiated cells increased in a dose-dependent manner and was the highest at 4 Gy (t = 17.356, p < 0.05). The transwell assays showed significantly decreased migration and invasion of both ray-irradiated cells compared with the 0 Gy control cells. The carbon ions of 2 and 4 Gy significantly inhibited A549 cell migration (t2Gy = 9.260, t4Gy = 19.052, both p < 0.05) and invasion compared with those in the control cells (t2Gy = 6.141, t4Gy = 12.700, both p < 0.05). Treatment with 2 and/or 4 Gy doses of carbon ion reduced GPX4 (t2Gy = 8.170, t4Gy = 13.811, both p < 0.05) and matrix metalloproteinase 2 (t2Gy = 207.620, t4Gy = 93.170, both p < 0.05) protein expression, but E-cadherin expression was increased (t2Gy = 62.811, t4Gy = 102.106, both p < 0.05). Conclusion Compared with X-ray irradiation, carbon ions have a higher relative biological effectiveness and can increase the proportion of A549 cells arrested in the G2/M stage to induce apoptosis, thereby inhibiting proliferation. At the same dose with X-ray, carbon ions may inhibit the migration and invasion of A549 cells by regulating the expression of GPX4, matrix metalloproteinase 2, and E-cadherin.