[6]-Gingerol Prevents Disassembly of Cell Junctions and Activities of MMPs in Invasive Human Pancreas Cancer Cells through ERK/NF- κ B/Snail Signal Transduction Pathway.
[6]-Gingerol Prevents Disassembly of Cell Junctions and Activities of MMPs in Invasive Human Pancreas Cancer Cells through ERK/NF- κ B/Snail Signal Transduction Pathway.
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DOI：
10.1155/2013/761852
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Kim MR
中科院分区：
文献类型：
--
作者：
Kim SO;Kim MR
为了研究[6]-姜酚（一种生姜植物化学物质）对紧密连接（TJ）分子的影响，我们研究了人胰腺导管细胞衍生的癌细胞系PANC-1中的TJ收紧和信号转导途径。采用MTT法测定细胞毒性;酶谱法测定基质金属蛋白酶（MMP）活性;跨上皮电阻（TER）和细胞旁流量测定TJ; RT-PCR和免疫印迹法测定TJ和侵袭相关蛋白; EMSA法测定PANC-1细胞NF-κB活性。结果显示，与对照组相比，TER显著增加，claudin 4和MMP-9降低。TJ蛋白水平，包括闭锁小带（ZO-）1，occludin，和E-钙粘蛋白，在[6]-姜酚处理的细胞中增加，这与细胞旁流量和MMP活性的降低相关。此外，NF-κB/Snail核转位通过下调细胞外信号调节激酶（ERK）途径被抑制，以响应[6]-姜辣素处理。此外，用ERK抑制剂U 0126处理完全阻断NF-κB活性。总之，这些研究结果表明，[6]-姜辣素通过抑制ERK途径抑制NF-κB/Snail来调节TJ相关蛋白并抑制侵袭和转移。因此，[6]-姜辣素可能抑制PANC-1细胞的侵袭活性。
To study the effects of [6]-gingerol, a ginger phytochemical, on tight junction (TJ) molecules, we investigated TJ tightening and signal transduction pathways in human pancreatic duct cell-derived cancer cell line PANC-1. The following methods were utilized: MTT assay to determine cytotoxicity; zymography to examine matrix metalloproteinase (MMP) activities; transepithelial electrical resistance (TER) and paracellular flux for TJ measurement; RT-PCR and immunoblotting for proteins related to TJ and invasion; and EMSA for NF-κB activity in PANC-1 cells. Results revealed that TER significantly increased and claudin 4 and MMP-9 decreased compared to those of the control. TJ protein levels, including zonula occludens (ZO-) 1, occludin, and E-cadherin, increased in [6]-gingerol-treated cells, which correlated with a decrease in paracellular flux and MMP activity. Furthermore, NF-κB/Snail nuclear translocation was suppressed via downregulation of the extracellular signal-regulated kinase (ERK) pathway in response to [6]-gingerol treatment. Moreover, treatment with U0126, an ERK inhibitor, completely blocked NF-κB activity. In conclusion, these findings demonstrate that [6]-gingerol regulates TJ-related proteins and suppresses invasion and metastasis through NF-κB/Snail inhibition via inhibition of the ERK pathway. Therefore, [6]-gingerol may suppress the invasive activity of PANC-1 cells.
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影响因子：
3.8
作者：
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通讯作者：
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作者：
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影响因子：
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作者：
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DOI：
10.2478/v10035-012-0064-6
发表时间：
2012-08-01
期刊：
Polski przeglad chirurgiczny
影响因子：
--
作者：
Durlik, Marek;Gardian, Katarzyna
通讯作者：
Gardian, Katarzyna