Ginsenoside Rg3 sensitizes human non-small cell lung cancer cells to γ-radiation by targeting the nuclear factor-κB pathway.
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.
Department of Respiratory Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
Lei
L
Wang
Department of Biochemistry and Molecular Biology, School of Basic Medicine, Tianjin Medical University, Tianjin 300060, P.R. China.
Xiankui
X
Li
Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
Yi-Min
YM
Song
Department of Orthopedics, General Hospital of Pingdingshan Shenma Medical Group, Pingdingshan, Henan 467000, P.R. China.
Bin
B
Wang
Department of Respiratory Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
Fu-Rui
FR
Zhang
Department of Respiratory Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
Rui
R
Yang
Department of Respiratory Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
Hua-Qi
HQ
Wang
Department of Respiratory Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
Guo-Jun
GJ
Zhang
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy* / Q000235:genetics / Q000532:radiotherapy; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000532:radiotherapy; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D005720:Gamma Rays; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D036145:Ginsenosides / Q000008:administration & dosage*; D006801:Humans; D051379:Mice; D016328:NF-kappa B / Q000096:biosynthesis; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage*; D023041:Xenograft Model Antitumor Assays
D036145:Ginsenosides; D016328:NF-kappa B; D011838:Radiation-Sensitizing Agents; C097367:ginsenoside Rg3