Nano-diamino-tetrac (NDAT) inhibits PD-L1 expression which is essential for proliferation in oral cancer cells

Food Chem Toxicol. 2018 Oct:120:1-11. doi: 10.1016/j.fct.2018.06.058. Epub 2018 Jun 28.

Abstract

Programmed death-ligand 1 (PD-L1) is a critical regulator to defend tumor cells against immune surveillance. Thyroid hormone has been shown to induce PD-L1 expression in cancer cells. Its nano-particulated analogue, nano-diamino-tetrac (NDAT; Nanotetrac) is an anticancer/anti-angiogenic agent. In the current study, the inhibitory mechanism by which NDAT inhibited PD-L1 mRNA abundance and PD-L1 protein content in oral cancer cells was investigated. NDAT inhibited inducible PD-L1 expression and protein accumulation by the inhibition of activated ERK1/2 and PI3K. Knockdown PD-L1 also inhibited the proliferation of oral cancer cells which suggests that the inhibitory effect of NDAT on PD-L1 expression maybe is one of the critical mechanisms for NDAT-induced anti-proliferative effect in oral cancer cells.

Keywords: NDAT; Oral cancer; PD-L1; Proliferation; Thyroxine.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • B7-H1 Antigen / antagonists & inhibitors*
  • B7-H1 Antigen / genetics*
  • B7-H1 Antigen / metabolism
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Gene Expression / drug effects*
  • Gene Knockdown Techniques
  • Humans
  • MAP Kinase Signaling System / drug effects
  • Mouth Neoplasms / genetics
  • Mouth Neoplasms / metabolism
  • Mouth Neoplasms / pathology*
  • Nanoparticles*
  • Phosphoinositide-3 Kinase Inhibitors
  • Protein Kinase Inhibitors / pharmacology
  • RNA, Messenger / metabolism
  • Thyroxine / analogs & derivatives*
  • Thyroxine / pharmacology

Substances

  • Antineoplastic Agents
  • B7-H1 Antigen
  • CD274 protein, human
  • Phosphoinositide-3 Kinase Inhibitors
  • Protein Kinase Inhibitors
  • RNA, Messenger
  • tetraiodothyroacetic acid
  • Thyroxine