Sulfated polysaccharide of Sepiella Maindroni ink inhibits the migration, invasion and matrix metalloproteinase-2 expression through suppressing EGFR-mediated p38/MAPK and PI3K/Akt/mTOR signaling pathways in SKOV-3 cells

• Published in: International journal of biological macromolecules Vol. 107; no. Pt A; pp. 349 - 362
• Main Authors: Jiang, Wenjie, Cheng, Yanna, Zhao, Na, Li, Lian, Shi, Yikang, Zong, Aizhen, Wang, Fengshan
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.02.2018
• Subjects: Animals; Cell Extracts - chemistry; Cell Line, Tumor; Cell Proliferation - drug effects; Decapodiformes - chemistry; Epidermal growth factor receptor/p38 MAPK/PI3K/Akt/mTOR pathway; Female; Gene Expression Regulation, Neoplastic; Humans; Matrix Metalloproteinase 2 - genetics; Matrix Metalloproteinase 9 - genetics; Matrix metalloproteinase-2; Neoplasm Invasiveness - genetics; Neoplasm Invasiveness - pathology; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - genetics; p38 Mitogen-Activated Protein Kinases - genetics; Polysaccharides - chemistry; Polysaccharides - isolation & purification; Polysaccharides - pharmacology; Proto-Oncogene Proteins c-akt - genetics; Receptor, Epidermal Growth Factor - genetics; Signal Transduction - drug effects; Sulfated polysaccharide of Sepiella maindroni ink; Sulfates - chemistry; TOR Serine-Threonine Kinases - genetics; Sulfated polysaccharide of Sepiella maindroni ink; Matrix metalloproteinase-2; Epidermal growth factor receptor/p38 MAPK/PI3K/Akt/mTOR pathway
• ISSN: 0141-8130; 1879-0003
• DOI: 10.1016/j.ijbiomac.2017.08.178

Previous studies demonstrated that SIP-SII, a sulfated derivative of SIP that is isolated from the ink of Sepiella maindroni, showed significant inhibition of tumor growth and metastasis. In this study, the effects of SIP-SII on the migration, invasion and molecular mechanism in ovarian cancer cell line, SKOV-3 cells, were investigated. The flow cytometry, confocal microscope observation, western blot and RT-PCR results indicated that SIP-SII located on cell membrane and inhibited the expression and activation of epidermal growth factor receptor (EGFR). Moreover, the binding capacity of SIP-SII with EGFR was confirmed by surface plasmon resonance (SPR) analysis and co-localization of EGFR and SIP-SII. Accordingly, SIP-SII was proved to attenuate the EGF-induced EGFR phosphorylation and migration by western blot and wound healing assay, respectively. Additionally, SIP-SII inhibited p38/MAPK and PI3K/Akt/mTOR signaling pathways in SKOV-3 cells significantly. What is more, SIP-SII showed amplified inhibitory activity on migration, invasion, and MMP-2 expression in combination with p38-specific inhibitor, PI3K-specific inhibitor or mTOR-specific inhibitor in SKOV-3 cells. Therefore, the mechanism that SIP-SII suppressed EGFR-mediated p38/MAPK and PI3K/Akt/mTOR signaling pathways to inhibit migration and invasion of SKOV-3 cells was demonstrated. These findings suggested that SIP-SII might be used as a potential inhibitor against tumor metastasis.