Effects of N-(4-hydroxyphenyl) Retinamide on Urokinase-type Plasminogen Activator and Plasminogen Activator Inhibitor-1 in Prostate Adenocarcinoma Cell Lines

Tanabe Tetsuyuki

Hiroshima Journal of Medical Sciences

[PISSN] 0018-2052

[EISSN] 2433-7668

[NCID] AA00664312

Previous investigations have demonstrated that a synthetic retinoid, N-(4-hydroxyphenyl) retinamide (4-HPR), inhibits the invasion of prostate adenocarcinoma in vitro. Urokinase-type plasminogen activator (uPA) is a prerequisite for tumor invasion. The purpose of this study was to evaluate the effects of 4-HPR on uPA and plasminogen activator inhibitor-1 (PAI-1) in prostate cancer.　　

Human prostate adenocacinoma cell lines, TSU-PR1 and PC3, were grown in serum-free media containing 4-HPR. Cellular mRNA and protein were subsequently extracted. Northern blot analysis, enzyme-linked immunosorbent assay (ELISA) and chromogenic functional analysis were performed on the samples.　　

Administration of 10-BM 4-HPR for 3 days resulted in an increase in uPA mRNA expression (TSU-PR1: 391 %, PC3: 356%), and a simultaneous increase in PAI-1 mRNA expression (TSUPR1: 217%, PC3: 235%) was observed. ELISA concomitantly demonstrated a significant increase (p<0.05) in uPA protein in the conditioned media (TSU-PR1: 134%, PC3: 139%) and cell lysates (TSU-PR1: 284%, PC3: 255%). Both cell lines demonstrated a significant increase (p<0.05) in PAI-1 protein in the conditioned media (TSU-PR1: 152%, PC3: 167%) and cell lysates (TSU-PR1: 170%, PC3: 222%). Concentrations below 10-sM failed to alter the protein production of either uPA or P AI-1. The functional uPA assay demonstrated a reduction of the proteolytic activity of uPA (TSU-PR1: 13%, PC3: 7%) in cell lysates of 10-BM 4-HPR (p<0.05), while there was minimal uPA activity in the conditioned media.　　

4-HPR stimulates a paradoxical increase in uPA and PAI-1, but the anti-invasive effects of 4-HPR are consistent with the increase in both uPA and PAI-1, resulting in an overall reduction of functional uPA activities.

Prostate cancer

4-HPR

uPA

PAl-1

Medical sciences [ 490 ]

eng

Hiroshima University Medical Press

[ISSN] 0018-2052

[NCID] AA00664312