Wang Subo, Cheng Yanna, Wang Fengshan, Sun Lirui, Liu Chunhui, Chen Guanjun, Li Yuhua, Ward S G, Qu Xianjun
School of Ocean Sciences, Shandong University at Weihai, Weihai 264209, China.
Biomed Pharmacother. 2008 Jun;62(5):297-302. doi: 10.1016/j.biopha.2008.01.018. Epub 2008 Feb 20.
SIP-SII is the sulfated S. maindroni ink polysaccharide (SIP) isolated from cuttlefish Sepiella maindroni. SIP-SII weakly inhibited tumor cell growth without cytotoxicity in vitro assay. Herein, we examined the effects of SIP-SII on the expression of matrix metalloproteinase MMP-2 and MMP-9 as well as tumor cell invasion and migration. SIP-SII (0.8-500 microg/ml) significantly decreased the expression of MMP-2 activity in human ovarian carcinoma cells SKOV3 as evidenced by the gelatin zymography analysis. No significant decrease of MMP-9 was detected in the cell line after SIP-SII treatment. The expression of MMP-2 was also evaluated using Western blot analysis. The results showed that SIP-SII inhibited the expression of MMP-2 in SKOV3 and human umbilical vein vascular endothelial cells ECV304 after 24 h incubation. Furthermore, the activity of invasion and migration of SKOV3 and ECV304 cells were measured. SIP-SII displayed an inhibitory effect on the penetration of SKOV3 cells through Matrigel-coated membrane in transwell chamber. A significant inhibition of ECV304 cell migration was observed in the presence of SIP-SII. These results suggest that SIP-SII might suppress invasion and migration of carcinoma cells via inhibition of MMP-2 proteolytic activity.
SIP - SII是从曼氏无针乌贼(Sepiella maindroni)中分离得到的硫酸化乌贼墨多糖(SIP)。在体外实验中,SIP - SII对肿瘤细胞生长有微弱抑制作用且无细胞毒性。在此,我们研究了SIP - SII对基质金属蛋白酶MMP - 2和MMP - 9表达以及肿瘤细胞侵袭和迁移的影响。明胶酶谱分析表明,SIP - SII(0.8 - 500微克/毫升)显著降低了人卵巢癌细胞SKOV3中MMP - 2的活性表达。SIP - SII处理后的细胞系中未检测到MMP - 9有显著降低。还使用蛋白质免疫印迹分析评估了MMP - 2的表达。结果显示,孵育24小时后,SIP - SII抑制了SKOV3和人脐静脉血管内皮细胞ECV304中MMP - 2的表达。此外,测量了SKOV3和ECV304细胞的侵袭和迁移活性。SIP - SII对SKOV3细胞穿透Transwell小室中基质胶包被的膜具有抑制作用。在存在SIP - SII的情况下,观察到ECV304细胞迁移受到显著抑制。这些结果表明,SIP - SII可能通过抑制MMP - 2蛋白水解活性来抑制癌细胞的侵袭和迁移。