title: Activation of liver X receptor inhibits the development of pulmonary carcinomas induced by 3-methylcholanthrene and butylated hydroxytoluene in BALB/c mice.
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.
authors.affiliation: Department of Neurosurgery, The General Hospital of Tianjin Medical University, Tianjin, China.|College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Qixue
authors.initials: Q
authors.lastname: Wang
authors.affiliation: College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Sun
authors.affiliation: College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Yang
authors.affiliation: College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Xingzhe
authors.initials: X
authors.lastname: Ma
authors.affiliation: College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Li
authors.affiliation: College of Biomedical Engineering, Hefei University of Technology, Hefei, China.|School of Medicine, Nankai University, Tianjin, China.
authors.forename: Yuanli
authors.initials: Y
authors.lastname: Chen
authors.affiliation: College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Di
authors.initials: D
authors.lastname: Zhang
authors.affiliation: College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Xiaoju
authors.initials: X
authors.lastname: Li
authors.affiliation: School of Medicine, Nankai University, Tianjin, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Xiang
authors.affiliation: Collaborative Innovation Center for Biotherapy, Sichuan University, Chengdu, China.
authors.forename: Yuquan
authors.initials: Y
authors.lastname: Wei
authors.affiliation: College of Biomedical Engineering, Hefei University of Technology, Hefei, China.|The State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences and Collaborative Innovation Center for Biotherapy, Nankai University, Tianjin, China.
authors.forename: Jihong
authors.initials: J
authors.lastname: Han
authors.affiliation: College of Biomedical Engineering, Hefei University of Technology, Hefei, China.|The State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences and Collaborative Innovation Center for Biotherapy, Nankai University, Tianjin, China.
authors.forename: Yajun
authors.initials: Y
authors.lastname: Duan
mesh_terms: D000818:Animals; D002084:Butylated Hydroxytoluene / Q000008:administration & dosage*; D002273:Carcinogens / Q000008:administration & dosage*; D002277:Carcinoma / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis / Q000097:blood; D000071518:Liver X Receptors / Q000378:metabolism*; D008168:Lung / Q000473:pathology; D008175:Lung Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D008748:Methylcholanthrene / Q000008:administration & dosage*; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016019:Survival Analysis
chemical_list: D002273:Carcinogens; D000071518:Liver X Receptors; D002084:Butylated Hydroxytoluene; D008748:Methylcholanthrene; D007371:Interferon-gamma