The saponin DT-13 inhibits gastric cancer cell migration through down-regulation of CCR5-CCL5 axis

• Published in: Chinese journal of natural medicines 2014-11, Vol.12 (11), p.833-840
• Main Authors: LIN, Sen-Sen, FAN, Wei, SUN, Li, LI, Fang-Fang, ZHAO, Ren-Ping, ZHANG, Lu-Yong, YU, Bo-Yang, YUAN, Sheng-Tao
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents, Phytogenic - pharmacology; BGC-823; CCL5; CCR5; Cell Movement - drug effects; Chemokine CCL5 - analysis; CXCR4; Down-Regulation; Gastric cancer cell migration; HGC-27; Humans; Liriope muscari; Neoplasm Metastasis - drug therapy; Receptors, CCR5 - analysis; Saponin DT-13; Saponins - pharmacology; Stomach Neoplasms - pathology; Tumor Cells, Cultured
• ISSN: 1875-5364; 1875-5364
• DOI: 10.1016/S1875-5364(14)60125-4

To investigate the effect of DT-13 on gastric cancer cell migration, and to explore the possible mechanisms underlying the anti-metastasis activity of DT-13. Growth inhibition of DT-13 was analyzed by the MTT assay. Cell migration was measured by the scratch-wound assay and transwell double chamber assay. To investigate the possible mechanisms underlying the anti-metastasis activity of DT-13, chemokine receptors that are involved in cancer metastasis (CCR2, CCR5, CCR7, CXCR4, and CXCR6) were detected by conventional PCR. The effect of DT-13 on CCR5 and CXCR4 expression was further evaluated by quantitative PCR and Western blot, respectively. The secretion of CCL5 (ligand of CCR5) and SDF-1 (ligand of CXCR4) were detected by enzyme-linked immunosorbent assay (ELISA). DT-13 inhibited BGC-823 and HGC-27 cell growth in a dose dependent manner, and the estimated IC50 value for 24 h treatment was 23.5 ± 5.1 μmol·L−1 for BGC-823 cells and 35.6 ± 7.6 μmol·L−1 for HGC-27 cells. DT-13 also significantly decreased gastric cancer cell migration. DT-13 significantly decreased the gene expression of CCR5 in both BGC-823 and HGC-27 gastric cancer cells, and moderately reduced the expression of CXCR4. Similar to the results of gene expression, significant down-regulation of CCR5 protein was observed, but CXCR4 protein levels were much less affected. CCL5 secretion, but not SDF-1 production, was inhibited by DT-13. DT-13 inhibited gastric cancer cell migration by down-regulation of the CCR5-CCL5 axis.