脂多糖（LPS）通过 TLR4/MyD88 信号通路增加胰腺癌细胞的侵袭能力。

Lipopolysaccharide (LPS) increases the invasive ability of pancreatic cancer cells through the TLR4/MyD88 signaling pathway.

机构信息

Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

出版信息

J Surg Oncol. 2009 Dec 15;100(8):725-31. doi: 10.1002/jso.21392.

DOI:10.1002/jso.21392

PMID:19722233

Abstract

BACKGROUND

Inflammation plays a multifaceted role in cancer progression, and NF-kappaB is one of the key factors connecting inflammation with cancer progression. We have shown that lipopolysaccharide (LPS) promotes NF-kappaB activation in colon cancer cells and pancreatic cancer cells. However, it is unclear why inflammatory stimuli can induce NF-kappaB activation in cancer cells.

METHODS

We used two human pancreatic cancer cells, Panc-1 and AsPC-1, as target cells. LPS was used as an inflammatory stimulus. To confirm the participation of TLR4/NF-kappaB signaling pathway, we used three different NF-kappaB inhibitors (PDTC, IkappaBalpha mutant, and NF-kappaB decoy ODN) and siRNAs (against TLR4, MyD88, and MMP-9). Effect of LPS on pancreatic cancer cell invasive ability was determined by Matrigel invasion assay.

RESULTS

LPS increased the invasive ability of pancreatic cancer cells, while blockade of NF-kappaB pathway decreased the LPS-dependent increased invasive ability. Blockade of TLR4 or MyD88 by siRNA also decreased the LPS-dependent increased invasive ability.

CONCLUSION

These results suggest that TLR/MyD88/NF-kappaB signaling pathway plays a significant role in connecting inflammation and cancer invasion and progression.

摘要

背景

炎症在癌症进展中起着多方面的作用，NF-κB 是连接炎症与癌症进展的关键因素之一。我们已经表明，脂多糖（LPS）可促进结肠癌和胰腺癌细胞中 NF-κB 的激活。然而，尚不清楚为什么炎症刺激可以诱导癌细胞中 NF-κB 的激活。

方法

我们使用两种人胰腺癌细胞系 Panc-1 和 AsPC-1 作为靶细胞。LPS 用作炎症刺激物。为了证实 TLR4/NF-κB 信号通路的参与，我们使用了三种不同的 NF-κB 抑制剂（PDTC、IκBα突变体和 NF-κB 诱饵 ODN）和 siRNA（针对 TLR4、MyD88 和 MMP-9）。通过 Matrigel 侵袭测定法确定 LPS 对胰腺癌细胞侵袭能力的影响。