BP-1-102 and silencing of Fascin-1 by RNA interference inhibits the proliferation of mouse pituitary adenoma AtT20 cells via the signal transducer and activator of transcription 3/fascin-1 pathway

Int J Neurosci. 2021 Aug;131(8):810-827. doi: 10.1080/00207454.2020.1758088. Epub 2020 May 18.

Abstract

Introduction: The expression levels of signal transducer and activator of transcription 3 (STAT3) protein and Fascin-1 were inhibited using the STAT3 inhibitor BP-1-102 and RNA interference, respectively, to investigate the expression of AtT20 in mouse pituitary cells. The proliferative capacity and related molecular mechanisms of pituitary tumor cells were then analyzed.

Methods: Mouse AtT20 pituitary adenoma cells were divided into a control group (Pa group), a STAT3 inhibitor vehicle group (PA + DMSO group), a STAT3 inhibitor group (PA + BP-1-102 group), a Fascin-1 negative control group (PA + neg-siRNA group) and a Fascin-1 silenced group (PA + Fascin-siRNA group). The related protein expression and cell proliferation of the five groups were measured using immunofluorescence, Western blot and real-time RT-PCR, whereas their apoptosis and cell cycle were evaluated using CCK-8 and flow cytometry.

Results: Proliferation of AtT20 cells is inhibited with BP-1-102 enhanced apoptosis, at the same time reduced the expression of Fascin-1 and N-cadherin, and increased the expression of E-cadherin. After inhibiting Fascin-1, the expression of STAT3 decreased, the expression of N-cadherin decreased and the expression of E-cadherin increased.

Conclusions: BP-1-102 is a novel drug with a great potential in pituitary tumors. Given their important roles in the growth of pituitary adenomas, STAT3 and Fascin-1 can be used as new treatment targets.

Keywords: AtT20; BP-1-102; E-cadherin; Fascin-1; N-cadherin; Pituitary adenoma; STAT3.

MeSH terms

  • Adenoma / metabolism*
  • Aminosalicylic Acids / administration & dosage
  • Animals
  • Cell Line, Tumor
  • Cell Proliferation* / drug effects
  • Mice
  • Microfilament Proteins / metabolism*
  • Pituitary Neoplasms / metabolism*
  • RNA Interference
  • Receptors, Odorant / metabolism*
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction / drug effects
  • Sulfonamides / administration & dosage

Substances

  • Aminosalicylic Acids
  • BP-1-102
  • Microfilament Proteins
  • Receptors, Odorant
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • Sulfonamides
  • fascin1 protein, mouse