Small molecule tolfenamic acid inhibits PC-3 cell proliferation and invasion in vitro, and tumor growth in orthotopic mouse model for prostate cancer†

摘要: BACKGROUND Specificity protein (Sp) transcription factors are implicated in critical cellular and molecular processes associated with cancer that impact tumor growth metastasis. The non-steroidal anti-inflammatory drug, tolfenamic acid (TA) is known to inhibit Sp proteins some human cells laboratory animal models. We evaluated the anti-cancer activity of TA using vitro vivo models for prostate cancer. METHODS The anti-proliferative efficacy was DU-145, PC-3, LNCaP cells. PC-3 were treated DMSO or 50 µM 48 hr. Whole cell lysates expression Sp1, survivin, c-PARP, Akt/p-Akt, c-Met, cdk4, cdc2, cyclin D3, E2F1 by Western blot analysis. Cell invasion assessed Boyden-chamber assay flow cytometry analysis used study apoptosis cycle distribution. An orthotopic mouse model PC-3-Luc effect TA. RESULTS TA inhibited p-Akt, survivin; increased c-PARP caspases caused arrest at G0/G1 phase accompanied a decrease an increase apoptotic markers. augmented annexin-V staining, caspase activity, indicating activation pathways. also decreased invasion. significantly weight volume which low Sp1 survivin sections. CONCLUSION TA targets pathways tumorigenesis These pre-clinical data strongly demonstrated cancer. Prostate 72:1648–1658, 2012. © 2012 Wiley Periodicals, Inc.