title: Fenofibrate exhibits a high potential to suppress the formation of squamous cell carcinoma in an oral-specific 4-nitroquinoline 1-oxide/arecoline mouse model.
abstract: The excessive use of areca nut and/or tobacco may induce the production of free radicals and reactive oxygen species, which affect the lipid contents of the cell membrane and are possibly involved in tumorigenic processes in the oral cavity. The aim of this study was to investigate the therapeutic efficacy of fenofibrate (0.1% or 0.3%, w/w), a ligand of the peroxisome proliferator-activated receptor alpha (PPARα), in a 4-nitroquinoline 1-oxide (4-NQO)/arecoline-induced oral cancer mouse model. The carcinogen, 4-NQO/arecoline, was administrated to C57BL/6JNarl mice for 8weeks followed by fenofibrate treatment for 12 or 20weeks. After 28weeks, changes in serum lipids, the multiplicity of tumor lesions, and tumor sizes were determined together with changes in the immunohistochemical expressions of PPARα, acetyl-coenzyme A carboxylase (ACC), the epidermal growth factor receptor (EGFR), and cyclooxygenase-2 (COX2). The results showed that when compared to the 4-NQO/arecoline only group, 0.3% fenofibrate treatment increased serum total cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels. 0.3% fenofibrate treatment suppressed the incidence rate of tongue lesions, reduced the multiplicity of squamous cell carcinoma (SCC), decreased the tumor size, and increased the immunoreactivity of EGFR and COX2 in oral dysplasia but decreased EGFR and COX2 expressions in SCC. These findings indicated that fenofibrate reduced the tumor incidence rate and suppressed the tumor progression into SCC and that these molecular events might be linked to the EGFR and COX2 regulatory pathways. We suggest that fenofibrate provides a new strategy for preventing oral tumor progression.
authors.affiliation: Department of Biochemistry, College of Medicine, China Medical University, Taichung, Taiwan, ROC.
authors.forename: Nai Wen
authors.initials: NW
authors.lastname: Chang
authors.forename: Ming-Hsui
authors.initials: MH
authors.lastname: Tsai
authors.forename: Chingju
authors.initials: C
authors.lastname: Lin
authors.forename: Hui Ting
authors.initials: HT
authors.lastname: Hsu
authors.forename: Pei-Yi
authors.initials: PY
authors.lastname: Chu
authors.forename: Chung-Min
authors.initials: CM
authors.lastname: Yeh
authors.forename: Chang-Fang
authors.initials: CF
authors.lastname: Chiu
authors.forename: Kun-Tu
authors.initials: KT
authors.lastname: Yeh
mesh_terms: D015112:4-Nitroquinoline-1-oxide; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D001115:Arecoline; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D011345:Fenofibrate / Q000627:therapeutic use*; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009062:Mouth Neoplasms / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D047493:PPAR alpha / Q000378:metabolism; D014059:Tongue / Q000187:drug effects / Q000473:pathology
chemical_list: D016588:Anticarcinogenic Agents; D000960:Hypolipidemic Agents; D008055:Lipids; D047493:PPAR alpha; D001115:Arecoline; D015112:4-Nitroquinoline-1-oxide; D051546:Cyclooxygenase 2; D066246:ErbB Receptors; D000103:Acetyl-CoA Carboxylase; D011345:Fenofibrate