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Toxicarioside A inhibits SGC-7901 proliferation, migration and invasion via NF-κB/bFGF signaling
Jun-Li Guo, Shao-Jiang Zheng, Yue-Nan Li, Wei Jie, Xin-Bao Hao, Tian-Fa Li, Li-Ping Xia, Wen-Li Mei, Feng-Ying Huang, Yue-Qiong Kong, Qi-Yi He, Kun Yang, Guang-Hong Tan, Hao-Fu Dai
Jun-Li Guo, Shao-Jiang Zheng, Yue-Nan Li, Xin-Bao Hao, Tian-Fa Li, Li-Ping Xia, Feng-Ying Huang, Yue-Qiong Kong, Qi-Yi He, Kun Yang, Guang-Hong Tan, Hainan Provincial Key Laboratory of Tropical Medicine, Cancer Research Institute of Affiliated Hospital, Hainan Medical College, Haikou 571199, Hainan Province, China
Wei Jie, Department of Pathology, Guangdong Medical College, Zhanjiang 524023, Guangdong Province, China
Wen-Li Mei, Hao-Fu Dai, Key Laboratory of Tropical Crop Biotechnology, Ministry of Agriculture, Institute of Tropical Bioscience and Biotechnology, Chinese Academy of Tropical Agricultural Sciences, Haikou 571101, Hainan Province, China
Author contributions: Guo JL, Zheng SJ and Li YN contributed equally to this work; Guo JL and Zheng SJ designed the research; Guo JL, Zheng SJ and Li YN performed the research with Jie W, Hao XB, Li TF, Xia LP, Mei WL, Huang FY; Li YN, Kong YQ, He QY and Yang K analyzed data; Zheng SJ and Guo JL wrote the manuscript; Tan GH and Dai HF revised and finally approved the article to be published.
Supported by Grants from the National Natural Scientific Foundation of China, No. 81060184; and the Natural Foundation of Hainan Province of China, No. 30864, 811201; and Program for New Century Excellent Talents in University of China, NCET-08-0657; and the National Basic Research Program of China, No. 2010CB534909; and Hainan Provincial Key Scientific Project, No. 061009
Correspondence to: Hao-Fu Dai, Professor, Key Laboratory of Tropical Crop Biotechnology, Ministry of Agriculture, Institute of Tropical Bioscience and Biotechnology, Chinese Academy of Tropical Agricultural Sciences, Haikou 571101, Hainan Province, China. hf_dai@yahoo.cn
Telephone: +86-898-66890292 Fax: +86-898-66890978
Received: September 10, 2011
Revised: January 17, 2012
Accepted: February 8, 2012
Published online: April 14, 2012
AIM: To investigate the inhibitory role of toxicarioside A on the gastric cancer cell line human gastric cancer cell line (SGC-7901) and determine the underlying molecular mechanism.
METHODS: After SGC-7901 cells were treated with toxicarioside A at various concentrations (0.5, 1.5, 4.5, 9.0 μg/mL) for 24 h or 48 h, cell viability was determined by 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay, and the motility and invasion of tumor cells were assessed by the Transwell chamber assay. Immunofluorescence staining, reverse transcription polymerase chain reaction and Western blotting were performed to detect the expression of basic fibroblast growth factor (bFGF) and fibroblast growth factor receptor-1 (FGFR1), and nuclear factor-kappa B (NF-κB) activation was examined by electrophoretic mobility shift assay.
RESULTS: The results showed that toxicarioside A was capable of reducing cell viability, inhibiting cell growth, and suppressing cell migration and invasion activities in a time- and dose-dependent manner in SGC-7901 cells. Further analysis revealed that not only the expression of bFGF and its high-affinity receptor FGFR1 but also the NF-κB-DNA binding activity were effectively blocked by toxicarioside A in a dose-dependent manner compared with the control group (P < 0.05 or P < 0.01). Interestingly, application of the NF-κB specific inhibitor, pyrrolidinedithiocarbamate (PDTC), to SGC-7901 cells significantly potentized the toxicarioside A-induced down-regulation of bFGF compared with the control group (P < 0.05).
CONCLUSION: These findings suggest that toxicarioside A has an anti-gastric cancer activity and this effect may be achieved partly through down-regulation of NF-κB and bFGF/FGFR1 signaling.
