Silibinin suppresses growth of human prostate carcinoma PC-3 orthotopic xenograft via activation of extracellular signal-regulated kinase 1/2 and inhibition of signal transducers and activators of transcription signaling.

摘要: Purpose: Silibinin is currently under phase II clinical trial in prostate cancer patients; however, its antitumor effects and mechanisms are not completely understood. Herein, we studied the efficacy associated of silibinin against orthotopically growing advanced human carcinoma PC-3 tumors. Experimental Design: Athymic male mice were implanted with cells 1 week later after surgical recovery gavaged daily (100 mg/kg body weight) for 7 weeks. Results: treatment reduced lower urogenital weight (including tumor, prostate, seminal vesicle) by 40% ( P = 0.02). Decreased levels cyclin-dependent kinases 2, 4, 6, CDC2, cyclins D1, D3, E, A observed, indicating an inhibitory effect on cell cycle progression. showed a tremendous increase extracellular signal-regulated kinase 1/2 phosphorylation but decreased c-Jun NH 2 -terminal p38 mitogen-activated protein phosphorylation. moderate decrease phosphorylated total Akt was also noted. marked signal transducers activators transcription (STAT) (Tyr 701 ), STAT1 (Ser 727 STAT3 705 STAT5 794 ) together their observed. Conclusions: These findings provide evidence tumor multitargeted mechanistic insights support investigation cancer.