Triptolide inhibits the migration and invasion of human prostate cancer cells via Caveolin-1/CD147/MMPs pathway

Biomed Pharmacother. 2016 Dec:84:1776-1782. doi: 10.1016/j.biopha.2016.10.104. Epub 2016 Nov 12.

Abstract

Prostate cancer (PCa) is the second most common type of carcinoma and the 5th leading cause of cancer-related death in males. Triptolide, is a main and effective component of Tripterygium wilfordii Hook F, which exerts an broad-spectrum anti-malignant tumor function. However, the effect of triptolide on migration and invasion of human prostate cancer cells is still poorly understood. In this study, we demonstrated that triptolide significantly inhibited the proliferation, migration and invasion of prostate cancer cells in a time- and dose-dependent manner. Caveolin-1 (Cav-1) is regarded as a major structural protein of caveolae and participated in lipid transport, signal transduction and tumor progression. Triptolide treatment inhibited the expression of tumor promoter Cav-1 and reduced CD147 and MMPs activities at both mRNA and protein levels. Meanwhile, triptolide treatment combined with Cav-1 knockdown in PCa cells enhanced the effects of anti-migration and anti-invasion, and those effects were restored following Cav-1-rescued. Together, our research indicates that triptolide represses the migration and invasion through Cav-1/CD147/MMPs pathway in PCa cells, which gives a better understanding of triptolide in clinical aggressive prostate cancer therapy.

Keywords: Invasion; Migration; Prostate cancer; Triptolide.

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Basigin / genetics
  • Basigin / metabolism*
  • Caveolin 1 / genetics
  • Caveolin 1 / metabolism*
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Cell Proliferation / drug effects
  • Diterpenes / pharmacology*
  • Dose-Response Relationship, Drug
  • Down-Regulation
  • Epoxy Compounds / pharmacology
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Matrix Metalloproteinases / genetics
  • Matrix Metalloproteinases / metabolism*
  • Neoplasm Invasiveness
  • Phenanthrenes / pharmacology*
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / enzymology
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / pathology
  • RNA Interference
  • Signal Transduction / drug effects
  • Time Factors
  • Transfection

Substances

  • Antineoplastic Agents, Phytogenic
  • BSG protein, human
  • CAV1 protein, human
  • Caveolin 1
  • Diterpenes
  • Epoxy Compounds
  • Phenanthrenes
  • Basigin
  • triptolide
  • Matrix Metalloproteinases