Inhibition of pancreatic adenocarcinoma cellular invasiveness by blebbistatin: a novel myosin II inhibitor
Inhibition of pancreatic adenocarcinoma cellular invasiveness by blebbistatin: a novel myosin II inhibitor
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DOI：
10.1016/j.bbrc.2003.12.031
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发表时间：
2004-01-23
影响因子：
3.1
通讯作者：
Whang, EE
中科院分区：
文献类型：
--
作者：
Duxbury, MS;Ashley, SW;Whang, EE
Blebbistatin 是一种新型 1-苯基-2-吡咯烷酮衍生物，能够高度特异性地抑制非肌肉肌球蛋白 II 活性。我们检查了肌球蛋白抑制剂对胰腺腺癌细胞迁移、侵袭、粘附和扩散的影响。布雷他汀剂量依赖性地抑制细胞迁移和侵袭，通过改良的博伊登室测定进行定量。基质金属蛋白酶 2 和 9 活性不受 blebbistatin 的影响，并且仅当 blebbistatin 的浓度超过抑制肌球蛋白 II 活性并干扰迁移和侵袭所需的浓度时，细胞增殖才会受到抑制。虽然肌球蛋白治疗不会影响细胞与细胞外基质成分纤连蛋白的粘附，但它显着损害了细胞在该基质上的铺展。原型纤连蛋白受体（α(5)β(1) 整合素）的细胞表面表达不受肌球蛋白抑制剂的影响。我们的观察结果说明了非肌肉肌球蛋白 II 在胰腺腺癌细胞侵袭和细胞外基质相互作用中的关键作用，并表明针对肌球蛋白 II 的治疗策略值得进一步研究。 (C) 2003 Elsevier Inc. 保留所有权利。
Blebbistatin is a novel 1-phenyl-2-pyrrolidinone derivative capable of inhibiting non-muscle myosin II activity with a high degree of specificity. We examined the effects of blebbistatin on pancreatic adenocarcinoma cellular migration, invasion, adhesion, and spreading. Blebbistatin dose-dependently inhibited cellular migration and invasiveness, quantified by modified Boyden chamber assay. Matrix metalloproteinase 2 and 9 activities were unaffected by blebbistatin and cellular proliferation was inhibited only by concentrations of blebbistatin exceeding those required to inhibit myosin II activity and to interfere with migration and invasion. While blebbistatin treatment did not affect cell adhesion to the extracellular matrix component fibronectin, it markedly impaired cell spreading on this substrate. Cell surface expression of the archetypal fibronectin receptor (alpha(5)beta(1) integrin) was unaffected by blebbistatin. Our observations illustrate the critical role of non-muscle myosin II in pancreatic adenocarcinoma cellular invasiveness and extracellular matrix interaction and suggest that therapeutic strategies targeting myosin II warrant further investigation. (C) 2003 Elsevier Inc. All rights reserved.