Activation of liver X receptor inhibits the development of pulmonary carcinomas induced by 3-methylcholanthrene and butylated hydroxytoluene in BALB/c mice

Sci Rep. 2016 Jun 2:6:27295. doi: 10.1038/srep27295.

Abstract

We previously reported that LXR ligand, T0901317, inhibited the growth of inoculated Lewis lung carcinoma in C57BL/6 mice by activating IFN-γ production. However, the effects of T0901317 on carcinogen-induced pulmonary carcinomas remain unknown. In this study, we initially conducted a statistical analysis on the data of human lung cancer samples extracted from the TCGA database, and determined that survival rate/time of lung cancer patients and grade of lung adenocarcinoma were positively and negatively related to lung IFN-γ levels, respectively. We then determined the inhibitory effects of T0901317 on mouse pulmonary carcinomas induced by 3-methylcholanthrene (MCA) and butylated hydroxytoluene (BHT) or urethane. We found that T0901317 reduced morbidity and mortality in MCA/BHT-injected BALB/c mice by inhibiting lung adenocarcinoma. T0901317 also protected C57BL/6 mice, but not IFN-γ deficient (IFN-γ(-/-), C57BL/6 background) mice, against MCA/BHT-induced lung hyperplasia/inflammation. In addition, we determined that T0901317 inhibited urethane-induced lung tumors in BABL/c mice. Furthermore, we determined that T0901317 prevented metastasis of 4T1 breast cancer cells in BALB/c mice. Administration of T0901317 substantially increased serum IFN-γ levels and lung IFN-γ expression in BABL/c and C57BL/6 mice. Taken together, our study demonstrates that LXR inhibits MCA/BHT-induced pulmonary carcinomas in BABL/c mice and the inhibition is associated with induction of IFN-γ production.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Butylated Hydroxytoluene / administration & dosage*
  • Carcinogens / administration & dosage*
  • Carcinoma / chemically induced
  • Carcinoma / pathology
  • Carcinoma / prevention & control*
  • Humans
  • Interferon-gamma / analysis
  • Interferon-gamma / blood
  • Liver X Receptors / metabolism*
  • Lung / pathology
  • Lung Neoplasms / chemically induced
  • Lung Neoplasms / pathology
  • Lung Neoplasms / prevention & control*
  • Methylcholanthrene / administration & dosage*
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Survival Analysis

Substances

  • Carcinogens
  • Liver X Receptors
  • Butylated Hydroxytoluene
  • Methylcholanthrene
  • Interferon-gamma