Inhibition of EGF-induced migration and invasion by sulfated polysaccharide of Sepiella maindroni ink via the suppression of EGFR/Akt/p38 MAPK/MMP-2 signaling pathway in KB cells - 14/11/17
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Highlights |
• | Sulfated polysaccharide of Sepiella maindroni ink (SIP-SII) inhibited EGF-induced migration and invasion in KB cells. |
• | SIP-SII inhibited the EGF-induced MMP-2 expression markedly in KB cells. |
• | SIP-SII attenuated the EGF-induced migration and invasion of KB cells via suppressing the EGFR/Akt/p38 MAPK/MMP-2 pathway. |
Abstract |
SIP-SII, the sulfated Sepiella maindroni ink polysaccharide (SIP), has been manifested to possess anti-tumor and anti-metastasis activity in vivo and in vitro. In the present study, we evaluated its inhibitory effect on the epidermal growth factor (EGF)-induced migration and invasion of human epidermoid carcinoma cell (KB cell line) as well as the related signaling pathways. The results of MTT assay indicated that SIP-SII inhibited the proliferation of KB cells in a concentration and time dependent manner. Notably, the attenuation of cell growth by SIP-SII was enlarged in the presence of EGF. The wound healing assay and transwell invasion assay were used to evaluate the effect of SIP-SII on the EGF-induced migration and invasion of KB cells and the results showed that SIP-SII markedly attenuated the EGF-induced migration and invasion. Besides, the EGF-induced matrix metalloproteinase-2 (MMP-2) expression was also suppressed by SIP-SII. However, SIP-SII showed no significant inhibition of the EGF-induced matrix metalloproteinase-9 (MMP-9) expression. Further research revealed that SIP-SII decreased the EGF-induced phosphorylation of epidermal growth factor receptor (EGFR), Akt and p38, but no significant suppression on EGF-induced phosphorylation of extracellular signal-regulated kinase 1 and 2 (Erk1/2) and c-Jun N-terminal kinases (JNK) by SIP-SII treatment was observed. The involvement of EGFR/Akt/p38 pathway was confirmed by evidence that SIP-SII would enlarge the inhibitory effect of the specific signal pathway inhibitors. These results indicate that SIP-SII has the potential to be used as the inhibitor of tumor metastasis especially for cancers characterized by over-activation of EGF/EGFR signaling.
Le texte complet de cet article est disponible en PDF.Abbreviations : SIP, SIP-SII, EGF, MMPs, EGFR, Erk1/2, JNK, MAPKs
Keywords : Sulfated polysaccharide of Sepiella maindroni ink, Matrix metalloproteinase-2, Matrix metalloproteinase-9, Epidermal growth factor, EGFR/Akt/p38 MAPK pathway
Plan
Vol 95
P. 95-102 - novembre 2017 Retour au numéro
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