At present, it is elusive how
non-small cell lung cancer (NSCLC) develops resistance to γ-radiation; however, the
transcription factor nuclear factor-κB (NF-κB) and NF-κB-regulated gene products have been proposed as mediators.
Ginsenoside Rg3 is a steroidal
saponin, which was isolated from Panax ginseng.
Ginsenoside Rg3 possesses high pharmacological activity and has previously been shown to suppress NF-κB activation in various types of
tumor cell. Therefore, the present study aimed to determine whether Rg3 could suppress NF-κB activation in NSCLC cells and sensitize NSCLC to γ-radiation, using an NSCLC cell line and NSCLC xenograft. A clone formation assay and lung
tumor xenograft experiment were used to assess the
radiosensitizing effects of
ginsenoside Rg3. NF-κB/inhibitor of NF-κB (IκB) modulation was ascertained using an electrophoretic mobility shift assay and western blot analysis. NF-κB-regulated gene products were monitored by western blot analysis. The present study demonstrated that
ginsenoside Rg3 was able to sensitize A549 and H1299 lung
carcinoma cells to γ-radiation and significantly enhance the efficacy of
radiation therapy in C57BL/6 mice bearing a
Lewis lung carcinoma cell xenograft
tumor. Furthermore,
ginsenoside Rg3 suppressed NF-κB activation, phosphorylation of IκB
protein and expression of NF-κB-regulated gene products (
cyclin D1, c-myc,
B-cell lymphoma 2,
cyclooxygenase-2,
matrix metalloproteinase-9 and
vascular endothelial growth factor), a number of which were induced by
radiation therapy and mediate radioresistance. In conclusion, the results of the present study suggested that
ginsenoside Rg3 may potentiate the antitumor effects of
radiation therapy in NSCLC by suppressing NF-κB activity and NF-κB-regulated gene products, leading to the inhibition of
tumor progression.