Paeoniflorin inhibits the growth of bladder carcinoma via deactivation of STAT3

Acta Pharm. 2018 Jun 1;68(2):211-222. doi: 10.2478/acph-2018-0013.

Abstract

Bladder cancer (BCa) is one of the most common urinary cancers. The present study aims to investigate whether Paeoniflorin (Pae) can exert inhibitory effects on BCa. The results showed that Pae inhibited proliferation of human BCa cell lines in a concentration- and time-dependent manner. Pae and cisplatin (Cis) synergistically inhibited the growth of tumours in RT4-bearing mice. Pae treatment neutralized the body loss induced by Cis. Moreover, Pae induced apoptosis in RT4 cells and increased the activities of caspase3, caspase8 and caspase9. Western blotting and immunohistochemical analysis revealed that the phosphorylated signal transducer and activator of transcription-3 (p-STAT3) level were decreased in Pae-treated RT4 cells and Pae-treated tumour-bearing mice. Furthermore, STAT3 transcriptional target B-cell lymphoma-2 was decreased in Pae-treated RT4 cells. Interestingly, Pae prevented translocation of STAT3 to the nucleus in RT4 cells. Collectively, Pae inhibits the growth of BCa, at least in part, via a STAT3 pathway.

Keywords: Radix Paeoniae alba; STAT3; apoptosis; bladder cancer; paeoniflorin.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / administration & dosage
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cisplatin / administration & dosage
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Glucosides / administration & dosage
  • Glucosides / pharmacology*
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Monoterpenes / administration & dosage
  • Monoterpenes / pharmacology*
  • Phosphorylation / drug effects
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction / drug effects
  • Time Factors
  • Urinary Bladder Neoplasms / drug therapy*
  • Urinary Bladder Neoplasms / pathology
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents, Phytogenic
  • Glucosides
  • Monoterpenes
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • peoniflorin
  • Cisplatin