Aryl Hydrocarbon Receptor Mediates Cell Proliferation Enhanced by Benzo[a]pyrene in Human Lung Cancer 3D Spheroids

Cancer Invest. 2019;37(8):367-375. doi: 10.1080/07357907.2019.1655760. Epub 2019 Aug 29.

Abstract

The aryl hydrocarbon receptor (AhR) is activated by the ligand, benzo[a]pyrene (B[a]P), a component of smoke that is implicated in lung carcinogenesis in humans. However, the role of B[a]P and AhR in lung cancer malignancy is not well known. In this study, we analyzed the effects of B[a]P and AhR in the 3 D spheroids of human lung cancer cells in vitro. In these spheroids, B[a]P and AhR enhanced cancer cell proliferation. These results suggest that the AhR-dependent effects of B[a]P on cell proliferation may contribute to the adverse effects of continuous smoking with respect to lung cancer malignancy.

Keywords: 3D spheroid; Lung cancer; aryl hydrocarbon receptor; benzo[a]pyrene; cell proliferation.

MeSH terms

  • A549 Cells
  • Adenocarcinoma of Lung / genetics
  • Adenocarcinoma of Lung / metabolism*
  • Adenocarcinoma of Lung / pathology
  • Basic Helix-Loop-Helix Transcription Factors / agonists*
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Benzo(a)pyrene / toxicity*
  • Cell Proliferation / drug effects*
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Receptors, Aryl Hydrocarbon / agonists*
  • Receptors, Aryl Hydrocarbon / genetics
  • Receptors, Aryl Hydrocarbon / metabolism
  • Signal Transduction
  • Spheroids, Cellular

Substances

  • AHR protein, human
  • Basic Helix-Loop-Helix Transcription Factors
  • Receptors, Aryl Hydrocarbon
  • Benzo(a)pyrene