JQ1, a BET-bromodomain inhibitor, inhibits human cancer growth and suppresses PD-L1 expression

Cell Biol Int. 2019 Jun;43(6):642-650. doi: 10.1002/cbin.11139. Epub 2019 Apr 25.

Abstract

Most traditional cytotoxic chemotherapeutic agents have poor aqueous solubility and significant toxicity. Hence, there is a need to develop molecule-targeted drugs. Programmed death-ligand 1 (PD-L1) is associated with the prognosis of several cancer types, and blockade of PD-1/PD-L1 signaling increases the amplitude of anti-tumor immunity. In the present study, we investigated the effects of JQ1, a bromodomain and extraterminal-bromodomain inhibitor, on cell growth, and messenger RNA (mRNA) and protein levels of PD-L1 in renal cell carcinoma primary culture cells, and prostate, liver, and lung cancer cell lines. The results of the cell counting kit-8 assay suggested that JQ1 inhibits cell growth in a dose-dependent manner. The mRNA and protein levels of PD-L1 decreased in the primary culture of JQ1-treated renal carcinoma, prostate cancer, liver cancer, and lung cancer cell lines. In addition, the mRNA level of PD-L2 also decreased in the JQ1-treated cells. Overall, JQ1 might be a potential anti-tumor agent.

Keywords: JQ1; PD-L1; cancer; growth.

MeSH terms

  • Azepines / metabolism
  • Azepines / pharmacology*
  • B7-H1 Antigen / antagonists & inhibitors*
  • B7-H1 Antigen / biosynthesis
  • B7-H1 Antigen / genetics
  • Carcinoma, Renal Cell / genetics
  • Carcinoma, Renal Cell / metabolism*
  • Cell Cycle / drug effects
  • Cell Line, Tumor / drug effects
  • Cell Proliferation / drug effects
  • Gene Expression / drug effects
  • Humans
  • Neoplasms / drug therapy*
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Primary Cell Culture
  • RNA, Messenger
  • Signal Transduction / drug effects
  • Triazoles / metabolism
  • Triazoles / pharmacology*

Substances

  • (+)-JQ1 compound
  • Azepines
  • B7-H1 Antigen
  • CD274 protein, human
  • RNA, Messenger
  • Triazoles