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Inhibition of pancreatic adenocarcinoma cellular invasiveness by blebbistatin: a novel myosin II inhibitor.

Abstract：

: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.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Duxbury MS,Ashley SW,Whang EE

doi

10.1016/j.bbrc.2003.12.031

subject

Has Abstract

pub_date

2004-01-23 00:00:00

pages

992-7

issue

4

eissn

0006-291X

issn

1090-2104

pii

S0006291X03026263

journal_volume

313

pub_type

杂志文章

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