DDTC Suppresses Ovarian Cancer Development via the PI3K/AKT/mTOR Signaling Pathway

Dis Markers. 2022 Aug 8;2022:1941077. doi: 10.1155/2022/1941077. eCollection 2022.

Abstract

In prior research, 6,12-diphenyl-3,9-diazatetraasterane-1, 5, 7, 11-tetracarboxylate (DDTC) has been shown to be an effective inhibitor of the growth of the SKOV3 and A2780 ovarian cancer (OC) cell lines. Flow cytometry analyses indicated that DDTC was able to suppress P-CNA expression at the protein level within OC cells, while RNA-seq indicated that DDTC treatment was associated with marked changes in gene expression profiles within A2780 cells. Molecular docking analyses suggested that DDTC has the potential to readily dock with key signaling proteins including PI3K, AKT, and mTOR. In line with these findings, DDTC treatment inhibited the growth of xenograft tumors in a mouse model system. Such treatment was also associated with reduced p-PI3K/PI3K, p-AKT/AKT, p-mTOR/mTOR, and CyclinD1 (CCND1) expressions and with the increased expression of PTEN in vitro and in vivo. Together, these results suggest that DDTC is capable of readily inhibiting OC development at least in part via targeting and modulating signaling via the PI3K/AKT/mTOR axis.

MeSH terms

  • Animals
  • Apoptosis
  • Carcinoma, Ovarian Epithelial
  • Cell Line, Tumor
  • Cell Proliferation
  • Female
  • Humans
  • Mice
  • Molecular Docking Simulation
  • Ovarian Neoplasms* / pathology
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt* / metabolism
  • Signal Transduction
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • MTOR protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases