The effects of PK11195 on meningioma was associated with allopregnanolone biosynthesis, which was mediated by translocator protein 18 KDa

Cancer Biomark. 2016;16(1):65-9. doi: 10.3233/CBM-150541.

Abstract

Meningioma is one of the common brain tumors in adults. It had been shown that the allopregnanolone biosynthesis was associated with tumorigenesis and PK11195, the translocator protein 18 KDa (TSPO) antagonist, had the effects of the allopregnanolone biosynthesis. However, little is known about the association between the effects of PK11195 on meningioma and the allopregnanolone biosynthesis. To evaluate this, the meningioma cell line IOMM-LEE was applied. Cell viability and proliferation were determined by CCK-8 assay. The IC50 of PK11195 on the IOMM-LEE was 1.505 ± 0.08 nM. The cell viability and proliferation of AC-5216 (TSPO selective ligand, 2 and 4 nM) was blocked by PK11195 (1.5 nM). Further, we evaluated the role of allopregnanolone biosynthesis in the effects of TSPO on meningioma. Enzyme-Linked ImmunoSorbent Assay (ELISA) was used in the measurement of the allopregnanolone level. It showed that the allopregnanolone level was increased by AC-5216 (2 and 4 nM) and the increase was reversed by PK11195 (1.5 nM). Collectedly, it firstly indicated that the effects of PK11195 on meningioma were relevant to the decrease of allopregnanolone biosynthesis, which was mediated by TSPO.

Keywords: AC-5216; PK11195; TSPO; allopregnanolone; meningioma.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Brain Neoplasms / metabolism*
  • Cell Line, Tumor
  • Drug Resistance, Neoplasm*
  • Humans
  • Isoquinolines / pharmacology*
  • Meningioma / metabolism*
  • Pregnanolone / biosynthesis*
  • Receptors, GABA / metabolism*

Substances

  • Antineoplastic Agents
  • Isoquinolines
  • Receptors, GABA
  • TSPO protein, human
  • Pregnanolone
  • PK 11195