Effects of STAT3 Inhibitor BP-1-102 on The Proliferation, Invasiveness, Apoptosis and Neurosphere Formation of Glioma Cells in Vitro

Cell Biochem Biophys. 2022 Dec;80(4):723-735. doi: 10.1007/s12013-022-01088-y. Epub 2022 Aug 22.

Abstract

Malignant glioma, especially glioblastoma (GBM), has historically been associated with a low survival rate. The hyperactivation of STAT3 played a key role in GBM initiation and resistance to therapy; thus, there is an urgent requirement for novel STAT3 inhibitors. BP-1-102 was recently reported as a biochemical inhibitor of STAT3, but its roles and mechanism in biological behavior of glioma cells were still unclear. In this study, the effects of BP-1-102 on proliferation, apoptosis, invasion and neurosphere formation of glioma cell were investigated. Our results indicated that BP-1-102 inhibited the proliferation of U251 and A172 cells, and their IC50 values were 10.51 and 8.534 μM, respectively. Furthermore, BP-1-102 inhibited the invasion and migration abilities of U251 and A172 cells by decreasing the expression of matrix metallopeptidase 9, and induced glioma cell apoptosis by decreasing the expression of B-cell lymphoma-2. BP-1-102 also inhibited the formation of neurosphere. Mechanically, BP-1-102 reduced the phosphorylation of STAT3 and the p-STAT3's nuclear translocation in glioma cells. Thus, this study herein provided a potential drug for glioma therapy.

Keywords: Apoptosis; BP-1-102; Glioma; Invasion; Proliferation; STAT3.

MeSH terms

  • Aminosalicylic Acids
  • Apoptosis
  • Brain Neoplasms* / metabolism
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Glioblastoma*
  • Glioma* / metabolism
  • Humans
  • Metalloproteases / metabolism
  • Metalloproteases / pharmacology
  • Neoplasm Invasiveness / prevention & control
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • STAT3 Transcription Factor / metabolism
  • Sulfonamides

Substances

  • Aminosalicylic Acids
  • BP-1-102
  • Proto-Oncogene Proteins c-bcl-2
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Sulfonamides
  • Metalloproteases