Enhancement of radiosensitivity by CpG-oligodeoxyribonucleotide-7909 in human non-small cell lung cancer A549 cells.
CpG-oligodeoxyribonucleotides (CpG-ODNs), which induce signaling through the toll-like receptor 9, are currently under investigation as immunity stimulators against cancer. It has recently been suggested that CpG-ODNs may also enhance sensitivity to traditional therapies including chemotherapy in certain cancer-cell lines. The purpose of this study was to define the activity of CpG-ODN7909 in increasing radiosensitivity of the human non-small cell lung cancer cell line A549 in vitro. First, a dose- and time-dependent inhibitory effect on cell viability was observed after A549 cells were treated with different concentrations of CpG-ODN7909 (5, 10, 30, and 60 microg/mL). Second, decreased cell clonogenic survival, enhanced cell apoptotic index, accumulated percentage of cells in the G2/M phase, and increased tumor necrosis factor (TNF)-alpha secretion were found after combined treatments with 10 microg/mL of CpG-ODN7909 and radiation compared to either treatment alone (p < 0.05). Furthermore, the toll-like receptor 9 mRNA was found to express in A549. The results suggest that CpG-ODN7909 can increase the radiosensitivity of human non-small cell lung cancer A549 cells, which may be associated with reduced cell clonogenic survival, enhanced apoptosis, prolonged cell-cycle arrest in G2/M, and stimulation of TNF-alpha secretion.
Zha
Lin
L
Department of Radiotherapy Oncology, Jinshan Hospital, Medical Center of Fudan University, Shanghai, People's Republic of China.
Qiao
Tiankui
T
Yuan
Sujuan
S
Lei
Linjie
L
D017209:Apoptosis / Q000528:radiation effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000473:pathology* / Q000532:radiotherapy*; D002453:Cell Cycle; D049109:Cell Proliferation; D003114:Colony-Forming Units Assay; D005720:Gamma Rays; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage* / Q000494:pharmacology; D011836:Radiation Tolerance / Q000235:genetics*; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage* / Q000494:pharmacology; D051217:Toll-Like Receptor 9 / Q000235:genetics; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
C408982:CPG-oligonucleotide; D009838:Oligodeoxyribonucleotides; D011838:Radiation-Sensitizing Agents; D051217:Toll-Like Receptor 9; D014409:Tumor Necrosis Factor-alpha