title: Fasudil inhibits lung carcinoma-conditioned endothelial cell viability             and migration.
abstract: The aim of this study was to investigate the effect of fasudil on lung carcinoma-conditioned             endothelial cells (LCc‑ECs). To obtain LCc-ECs, human umbilical vein endothelial             cells (HUVECs) were treated with conditioned cell culture media from human A549             lung adenocarcinoma cells. The effect of fasudil on the viability of LCc-ECs was             assessed using the MTT assay, in vitro invasive ability was evaluated using the             transwell chamber assay and cytoskeletal changes were detected using fluorescein-labelled             phalloidin immunocytochemistry. RhoA mRNA and p-MLC protein expression were measured             using RT-PCR and western blotting. Fasudil significantly and dose-dependently             inhibited LCc-EC proliferation and in vitro invasive ability. Fasudil also led             to stress fibre breakage and fracture in LCc-ECs, indicating that fasudil impacts             polymerisation of the cytoskeletal actin filament network. Expression of RhoA             mRNA and protein expression of the ROCK substrate p-MLC were reduced by fasudil,             suggesting that fasudil can inhibit RhoA/ROCK signalling and attenuate angiogenesis             in LCc-ECs. This study indicates that fasudil is an anti-angiogenic agent with             potential application for the treatment of cancer, especially lung adenocarcinoma.
authors.affiliation: Department of Integrated Therapy, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai 200032, PR China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zhang
authors.forename: Jing-Hua
authors.initials: JH
authors.lastname: Ren
authors.forename: Zhen-Yu
authors.initials: ZY
authors.lastname: Li
authors.forename: Li
authors.initials: L
authors.lastname: Nong
authors.forename: Gang
authors.initials: G
authors.lastname: Wu
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000230:Adenocarcinoma / Q000378:metabolism*; D000077192:Adenocarcinoma of Lung; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D022502:Stress Fibers / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors; D020742:rhoA GTP-Binding Protein / Q000235:genetics
chemical_list: D020533:Angiogenesis Inhibitors; D017077:Culture Media, Conditioned; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein; C049347:fasudil