Resveratrol attenuates matrix metalloproteinase-9 and-2-regulated differentiation of HTB94 chondrosarcoma cells through the p38 kinase and JNK pathways
Resveratrol attenuates matrix metalloproteinase-9 and-2-regulated differentiation of HTB94 chondrosarcoma cells through the p38 kinase and JNK pathways
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DOI：
10.3892/or.2014.3192
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发表时间：
2014-07-01
期刊：
影响因子：
4.2
通讯作者：
Kim, Song-Ja
中科院分区：
文献类型：
--
作者：
Gweon, Eun Jeong;Kim, Song-Ja
白藜芦醇已被证明具有抗癌，抗衰老和抗炎特性。基质金属蛋白酶（MMP）似乎是负责在癌症，衰老和炎症的进展中观察到的细胞外基质（ECM）降解的大部分。我们发现，白藜芦醇显着抑制MMP-2和MMP-9，并诱导II型胶原和性别决定区Y-box（SOX）-9的表达和硫酸化蛋白多糖的产生在HTB 94软骨肉瘤细胞。此外，用MMP抑制剂抑制MMP进一步增强了白藜芦醇的作用。白藜芦醇可增加p38的磷酸化，抑制c-Jun N-末端激酶（JNK）的磷酸化。用SB 203580（一种p38激酶抑制剂）治疗增强了白藜芦醇对MMP-2和MMP-9的抑制，并抑制了白藜芦醇诱导的II型胶原和SOX-9表达的刺激以及硫酸化蛋白多糖的产生。用JNK抑制剂SP 600125处理，减弱了白藜芦醇对MMP-2和MMP-9的作用，并加速了白藜芦醇诱导的对II型胶原、SOX-9和硫酸化蛋白多糖产生的作用。我们的研究结果表明，白藜芦醇抑制MMP诱导分化通过p38激酶和JNK途径在HTB 94软骨肉瘤细胞。
Resveratrol has been shown to possess anticancer, anti-aging, and anti-inflammatory properties. Matrix metalloproteinases (MMPs) appear to be responsible for much of the extracellular matrix (ECM) degradation observed in the progression of cancer, aging and inflammation. We found that resveratrol significantly inhibited MMP-2 and MMP-9, and induced the expression of type II collagen and sex-determining region Y-box (SOX)-9 and the production of sulfated proteoglycans in HTB94 chondrosarcoma cells. Moreover, inhibition of MMPs with an MMP inhibitor further enhanced the effects of resveratrol. Phosphorylation of p38 was increased and phosphorylation of c-Jun N-terminal kinase (JNK) was inhibited by resveratrol. Treatment with SB203580, a p38 kinase inhibitor, enhanced the suppression of MMP-2 and MMP-9 by resveratrol and inhibited resveratrol-induced stimulation of type II collagen and SOX-9 expression and production of sulfated proteoglycans. Treatment with SP600125, a JNK inhibitor, attenuated the effects of resveratrol on MMP-2 and MMP-9, and accelerated resveratrol-induced effects on type II collagen, SOX-9 and sulfated proteoglycan production. Our results suggest that resveratrol inhibits MMP-induced differentiation via the p38 kinase and JNK pathways in HTB94 chondrosarcoma cells.