1.Department of Oncology,the Affiliated Xisoshan Hospital of Hangzhou Normal University, Hangzhou 311201, China; 2.Department of Radiotherapy, the Affiliated Xisoshan Hospital of Hangzhou Normal University, Hangzhou 311201, China
JIANG Yiling,YU Hongjin,ZHANG Ningbo, et al. Mechanism of allicin in enhancing radiosensitivity of non-small cell lung cancer A549 cells via miR-486-5p/KDM5B axis[J]. JOURNAL OF WEZHOU MEDICAL UNIVERSITY, 2022, 52(5): 358-364.
Abstract：Objective: To investigate the effect of allicin on the radiosensitivity of non-small cell lung cancer (NSCLC) cell line A549 and its underlying mechanisms. Methods: A549 cells were posed to X-rays in the presence or absence of allicin. The proliferation of A549 cells was detected by 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay. Transwell assay was performed to detect the invasive ability of A549 cells. Clonogenic survival assay was used to evaluate cell radiosensitivity in A549 cells. DNA damage in A549 cells was assessed by comet assay. The protein level of γ-H2AX, Snail, Vimentin and lysine demethylase 5B (KDM5B) in A549 cells was measured by Western blot. qRT-PCR was utilized to measure the expression of miR-549-5p. The dual-luciferase reporter gene assay was employed to verify the targeting relationship of miR-486-5p with HDM5B. Results: Treatment with different concentrations of allicin (20, 40, 60 μg/mL) significantly inhibited the proliferation (P<0.05) and invasion ability (P<0.05) of A549 cells, as well as upregulated miR-486-5p expression in A549 cells (P<0.05). Treatment with 40 μg/mL allicin significantly upregulated the inhibitory effect of X-rays on the proliferation and invasion ability of A549 cells (all P<0.05) and accelerated DNA damage in A549 cells. Mechanistically, allicin enhanced the sensitivity of A549 cells to X-rays by upregulating miR-486-5p expression, but knockdown of miR-486-5p significantly reversed the radiosensitizing effect of allicin on A549 cells. Furthermore, miR-486-5p could negatively regulate its targeted KDM5B expression. Conclusion: Allicin could enhance the sensitivity of A549 cells to X-rays by inhibiting cell proliferation, invasion and inducing cellular DNA damage, and its mechanism of action is achieved by upregulating the inhibitory effect of miR-486-5p on KDM5B expression.
