<p>Low-Dose Radiation Promotes Invasion and Migration of A549 Cells by Activating the CXCL1/NF-κB Signaling Pathway</p>

Abstract

Radiation has well-known and well-characterized direct toxic effects on cells and tissues. However, low-dose ionizing irradiation (LDIR) can also enhance the invasion and migration of tumor cells, and the mechanisms underlying these effects remain unclear. The present study aimed to investigate changes induced in the migration and invasion of A549 cells after LDIR and to explore the potential molecular mechanism. Materials and Methods: A549 cells were irradiated with X-rays at different doses (0, 2, 4, and 6 Gy) and cultured for 24 or 48 h. Apoptosis and proliferation were evaluated by lactate dehydrogenase release, CCK8, colony formation, and flow cytometry assays. Wound-healing and transwell assays were performed to detect migration and invasion ability. CXCL1 or p65 were knocked down using lentivirus-mediated siRNA in A549 cell lines. Knockdown efficiency of CXCL1 and p65 was assessed by RT-qPCR. Western blotting and immunofluorescence were used to determine the changes in protein levels. Results: In cells irradiated with a dose of 6 Gy, after 48 h, apoptosis was clearly induced while proliferation was inhibited. Irradiation with 4 Gy resulted in the upregulation of CXCL1 expression and activation of the NF-κB signaling pathway. Moreover, upon 4 Gy irradiation, migration, invasion, and epithelial-mesenchymal transition (EMT) were significantly enhanced in A549 cells. Importantly, CXCL1 or p65 knockdown inhibited radiationinduced migration, invasion, and EMT. Conclusion: Low-dose radiation upregulates CXCL1 expression and activates the NF-κB signaling to regulate EMT in A549 cells, thereby promoting invasion and migration. These results provide new insights into the prevention of tumor invasion and metastasis induced by radiotherapy.

Diallyl Disulfide Attenuates Ionizing Radiation-Induced Migration and Invasion by Suppressing Nrf2 Signaling in Non–small-Cell Lung Cancer

“…15,39 Despite great advances in radiotherapy techniques and modalities, recurrence and resistance still limit the therapeutic success. There is evidence that when tumor cells are exposed to low doses of X-rays, their viability and proliferation ability is significantly suppressed, while migration and invasion capabilities are significantly enhanced; [20][21][22] thus, seeking novel approaches or agents to reverse IR-induced tumor cell invasion and migration is the key to overcoming tumor recurrence and metastasis during radiotherapy for NSCLC. Diallyl disulfide, a major organosulfur compound derived from garlic, were reported to exhibit various pharmacological properties such as antibacteria, antiangiogenesis, anticancer, and anticoagulation.…”

“…9 Besides, DADS are also reported to induce cytotoxicity and induction of cell death in various human cancer cells. 7,21,40 It has been indicated that DADS could suppress cell migration and the invasion in human triple negative breast cancer, 7 colorectal cancer, 20 colon cancer 9,41 and prostate cancer cells. 11 Recently, studies showed that DADS inhibited human colon cancer cell growth, invasion and migration, and reversed the EMT in gastric cancer cells 42 and A549 lung cancer cells.…”

“…19 Due to when tumor cells are exposed to low doses of X-rays, their proliferation ability is significantly suppressed, while migration and invasion capabilities are significantly enhanced. [20][21][22] Although DADS were previously reported to enhance radiation-induced apoptosis and suppress cancer cell proliferation in cervical cancer cells, 23 the effect of DADS on radiation-induced migration and invasion of NSCLC and its molecular mechanisms are currently unknown.…”

Hyaluronic Acid-modified Redox-sensitive Hybrid Nanocomplex Loading With siRNA for Non-small-cell Lung Carcinoma Therapy

“…A549 cells were seeded in 6-well plates at a density of 2 × 10 5 cells/well and cultured 24 h to reach 90% con uence as a monolayer. Then the monolayer was scratched with a sterile pipette tip (200 µL type) and washed with PBS twice [41,42]. The cells were treated by the complexes and continued to culture in DMEM containing 10 % FBS for 72 h and the wound areas were measured by microplate reader (Model 550, Bio-Rad, U.S.A) at 12, 24, 36, 48, 60 and 72 h, respectively.…”

“…After trypsinization, A549 cells were plated in the upper chamber inserted in 24-well plates with serum-free DMEM at a density of 2.0 × 10 4 cells/well, and DMEM with 10 % FBS was added into the lower chamber. After incubation for 24 h, cells in the upper chamber were wiped by cotton swab, and cells migrated to the lower surface were xed with ethanol at 4℃ for 15 min and stained with 0.2 % crystal violet for 30 min [41,42]. The stained cells were then rinsed with PBS and recorded by Olympus uorescence microscope.…”