The saponin DT-13 inhibits gastric cancer cell migration through down-regulation of CCR5-CCL5 axis.
10.1016/S1875-5364(14)60125-4
- Author:
Sen-Sen LIN
1
;
Wei FAN
1
;
Li SUN
2
;
Fang-Fang LI
1
;
Ren-Ping ZHAO
1
;
Lu-Yong ZHANG
1
;
Bo-Yang YU
3
;
Sheng-Tao YUAN
4
Author Information
1. New Drug Screen Center, China Pharmaceutical University, Nanjing 210009, China.
2. New Drug Screen Center, China Pharmaceutical University, Nanjing 210009, China. Electronic address: cpusunli@126.com.
3. Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing 211198, China.
4. New Drug Screen Center, China Pharmaceutical University, Nanjing 210009, China. Electronic address: yuanst@aliyun.com.
- Publication Type:Journal Article
- Keywords:
BGC-823;
CCL5;
CCR5;
CXCR4;
Gastric cancer cell migration;
HGC-27;
Liriope muscari;
Saponin DT-13
- MeSH:
Antineoplastic Agents, Phytogenic;
pharmacology;
Cell Movement;
drug effects;
Chemokine CCL5;
analysis;
Down-Regulation;
Humans;
Neoplasm Metastasis;
drug therapy;
Receptors, CCR5;
analysis;
Saponins;
pharmacology;
Stomach Neoplasms;
pathology;
Tumor Cells, Cultured
- From:
Chinese Journal of Natural Medicines (English Ed.)
2014;12(11):833-840
- CountryChina
- Language:English
-
Abstract:
AIM: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.
METHODS: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).
RESULTS: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.
CONCLUSION:DT-13 inhibited gastric cancer cell migration by down-regulation of the CCR5-CCL5 axis.
