Stigmasterol inhibits the progression of lung cancer by regulating retinoic acid-related orphan receptor C

Histol Histopathol. 2021 Dec;36(12):1285-1299. doi: 10.14670/HH-18-388. Epub 2021 Oct 29.

Abstract

Objective: This study aims to investigate the role of stigmasterol in lung cancer. The study aims to investigate the role of stigmasterol in lung cancer and further explore its possible mechanisms.

Methods: Cell Counting Kit-8 assay, 5-ethynyl-2-deoxyuridine (EdU), TUNEL and Flow cytometry were conducted to detect the proliferation and apoptosis of lung cancer cell lines. qRT-PCR and western blot were conducted to detect mRNA and protein levels of caspase-3 and caspase-9. In addition, Gene Ontology, STRING, SWISSMODEL, cellular thermal shift assay (CETSA) and Swiss Target Prediction were used to predict the targets of stigmasterol.

Results: Behavioral studies showed that stigmasterol inhibited the proliferation and promoted the apoptosis of lung cancer cells. Further research revealed that retinoic acid-related orphan receptor C (RORC) directly targeted stigmasterol in lung cancer. Interestingly, rescue experiments indicated that RORC overexpression reversed the inhibitory effect of stigmasterol on lung cancer.

Conclusion: In our study, we confirmed the functional role of the stigmasterol-RORC axis in lung cancer progression, which provides a latent target for lung cancer treatment.

MeSH terms

  • Apoptosis / drug effects*
  • Caspase 3
  • Caspase 9
  • Flow Cytometry
  • Humans
  • Lung Neoplasms / prevention & control*
  • Orphan Nuclear Receptors*
  • Receptors, Retinoic Acid / genetics
  • Receptors, Retinoic Acid / metabolism*
  • Stigmasterol / pharmacology*
  • Tretinoin / pharmacology

Substances

  • Orphan Nuclear Receptors
  • Receptors, Retinoic Acid
  • Tretinoin
  • Stigmasterol
  • CASP3 protein, human
  • CASP9 protein, human
  • Caspase 3
  • Caspase 9