Investigation of the relationship between an ATX inhibitor and the membrane lipid profiles of glioblastoma, prostate, and thyroid cancers, and its antiproliferative effect.

Project no. 32797 · Status: Kapanmış · 2025

Summary

<p>This&nbsp;study&nbsp;investigated&nbsp;the&nbsp;antiproliferative&nbsp;potential&nbsp;of&nbsp;inhibition&nbsp;of&nbsp;autotaxin&nbsp;(ATX),&nbsp;a&nbsp;lysophospholipase&nbsp;D&nbsp;that&nbsp;converts&nbsp;lysophosphatidylcholine&nbsp;(LPC)&nbsp;into&nbsp;lysophosphatidic&nbsp;acid&nbsp;(LPA)&nbsp;and&nbsp;thereby&nbsp;modulates&nbsp;LPA-dependent&nbsp;proliferation&nbsp;and&nbsp;migration&nbsp;signaling&nbsp;in&nbsp;cancer&nbsp;cells.&nbsp;A&nbsp;comparative&nbsp;design&nbsp;across&nbsp;glioblastoma,&nbsp;prostate&nbsp;and&nbsp;thyroid&nbsp;cell&nbsp;lines&nbsp;was&nbsp;originally&nbsp;planned;&nbsp;however,&nbsp;due&nbsp;to&nbsp;delayed&nbsp;procurement&nbsp;of&nbsp;cell&nbsp;lines&nbsp;and&nbsp;technical&nbsp;issues&nbsp;during&nbsp;culture,&nbsp;experiments&nbsp;were&nbsp;completed&nbsp;in&nbsp;the&nbsp;U87&nbsp;glioblastoma&nbsp;cell&nbsp;line&nbsp;only.&nbsp;Cytotoxicity&nbsp;of&nbsp;the&nbsp;ATX&nbsp;inhibitor&nbsp;HA130&nbsp;was&nbsp;assessed&nbsp;by&nbsp;the&nbsp;WST-1&nbsp;assay&nbsp;at&nbsp;24,&nbsp;48&nbsp;and&nbsp;72&nbsp;h,&nbsp;yielding&nbsp;IC₅₀&nbsp;values&nbsp;of&nbsp;120.10&nbsp;µM,&nbsp;110.8&nbsp;µM&nbsp;(r=0.96)&nbsp;and&nbsp;143&nbsp;µM,&nbsp;respectively.&nbsp;Cell&nbsp;migration&nbsp;was&nbsp;monitored&nbsp;using&nbsp;a&nbsp;scratch-wound&nbsp;assay,&nbsp;and&nbsp;HA130&nbsp;treatment&nbsp;delayed&nbsp;wound&nbsp;closure&nbsp;compared&nbsp;with&nbsp;untreated&nbsp;controls&nbsp;at&nbsp;48&nbsp;h.&nbsp;Membrane&nbsp;lipids&nbsp;were&nbsp;extracted&nbsp;using&nbsp;a&nbsp;modified&nbsp;Bligh-Dyer/Folch&nbsp;procedure&nbsp;and&nbsp;profiled&nbsp;by&nbsp;HPLC.&nbsp;HA130&nbsp;exposure&nbsp;decreased&nbsp;cholesterol&nbsp;esters&nbsp;while&nbsp;increasing&nbsp;free&nbsp;cholesterol&nbsp;and&nbsp;phosphatidylethanolamine;&nbsp;phosphatidylcholine&nbsp;and&nbsp;sphingolipids&nbsp;were&nbsp;not&nbsp;detectable&nbsp;under&nbsp;the&nbsp;applied&nbsp;conditions.&nbsp;Overall,&nbsp;the&nbsp;findings&nbsp;suggest&nbsp;that&nbsp;ATX&nbsp;inhibition&nbsp;may&nbsp;influence&nbsp;proliferation,&nbsp;migration&nbsp;and&nbsp;membrane&nbsp;lipid&nbsp;organization&nbsp;in&nbsp;U87&nbsp;cells,&nbsp;warranting&nbsp;further&nbsp;validation&nbsp;with&nbsp;additional&nbsp;cell&nbsp;models&nbsp;and&nbsp;orthogonal&nbsp;lipidomics&nbsp;approaches.</p>

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