Author of

• 11260

  +

  MO04 - Lung Cancer Biology I (ID 86)

  • Event: WCLC 2013
  • Type: Mini Oral Abstract Session
  • Track: Biology
  • Presentations: 1
  • Moderators:G. Sozzi, D.C. Lam
  • Coordinates: 10/28/2013, 16:15 - 17:45, Bayside 103, Level 1

  • 11268

    +

    MO04.08 - Activation of liver X receptor induces interferon-gamma production and inhibits tumor growth (ID 705)

    17:00 - 17:05  |  Author(s): Y. Duan
    • Abstract
    • Presentation
    • Slides

    Background
    Interferon-γ (IFN-γ) has been well documented to have multiple functions including anti-tumorigenesis. Liver X receptors α and β (LXR) are members of ligand- activated nuclear receptor superfamily. LXR can be ac- tivated by natural ligands of some oxysterols and by numerous synthetic ligands (e.g. T317).The LXR-induced ABCA1 expression promotes free cholesterol efflux from macrophages thereby inhibiting the development of atherosclerosis. LXR has also been demonstrated the important functions in immune system . Here we tested the hypothesis that IFN-γ is a target for LXR activation, and the induction of IFN-γ expression by LXR can lead to inhibition of tumor growth.

    Methods
    C57 wild type or IFN-γ-/- mice (same background) in two groups were s.c. injected with2×10 5 LLC1 cells (ATCC) in the right flank to establish a carcinoma tumor model. For carcinogen-induced tumor: at the first week, C57 mice were i.p. injected with MCA (15 mg/kg body); from the second week, the mice were i.p. weekly injected with BHT for 6 weeks. The doses of BHT were: 1st injection, 150 mg/kg body weight; 2nd to 6th injections, 200 mg/kg.

    Results
    In this study, we observed that LXR ligand (T317) induced IFN-γ protein expression which was associated with increased mRNA and secreted protein levels in culture medium. In vivo,T317 increased wild type mouse serum IFN-γ levels and IFN-γexpression in tissues. T317 inhibited the inoculated LLC1 tumor growth in wild type mice but not in IFN-γ knockout (IFN-γ-/-) mice. In addition, T317 displayed inhibitory and therapeutic effects on 3-methylcholanthrene/butylated hydroxytoluene (MCA/BHT)-induced pulmonary carcinomas. T317 inhibits the growth of inoculated LLC1 tumor in wild type mice but not in IFN-γ-/- mice Wild type or IFN-γ-/- mice. Figure 1 T1317 inhibits MCA/BHT-induced pulmonary tumors Figure 2

    Conclusion
    Our study demonstrates IFN-γ is a target gene of LXR activation. LXR-induced IFN-γ expression can be attributed, at least in part, to the anti-tumorigenic properties of LXR.

    Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

    Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.