title: Fenofibrate enhances radiosensitivity of esophageal squamous cell carcinoma by suppressing hypoxia-inducible factor-1α expression.
abstract: Radiation therapy is widely used in esophageal squamous cell carcinoma (ESCC). Promoting radiation sensitivity is important. Recent studies have shown that fenofibrate can inhibit the growth of several cancer lines and hypoxia-inducible factor-1α (HIF-1α) expression in MCF-7 cells. However, few studies on the radiosensitive effect of fenofibrate on ESCCs under hypoxic condition have been conducted. In this study, we assessed the radiosensitive effects of fenofibrate on human ESCC cells. In vitro experiments showed the inhibition of cytotoxic effects after ionizing irradiation. We measured cell viability and clonogenic survival rate. Flow cytometry showed that fenofibrate pretreatment promoted apoptosis. The in vivo data also suggest that fenofibrate had radiosensitizing effects in ECA-109 cells xenografted into nude mice. Western blot and immunohistochemical analyses revealed that the HIF-1α and vascular endothelial growth factor (VEGF) protein content decreased by fenofibrate. Thus, the inhibition of HIF-1α and VEGF expression in ESCC cells contributed to the radiosensitive effect. These data suggest that fenofibrate may be a potential radiosensitive drug.
authors: Department of Radiation Oncology, Nantong Tumor Hospital, Nantong University, Nantong, China.
authors: Yangyang
authors: Y
authors: Ge
authors: Jia
authors: J
authors: Liu
authors: Xi
authors: X
authors: Yang
authors: Hongcheng
authors: H
authors: Zhu
authors: Baixia
authors: B
authors: Yang
authors: Kuiling
authors: K
authors: Zhao
authors: Zhijun
authors: Z
authors: Wu
authors: Guojian
authors: G
authors: Cheng
authors: Feng
authors: F
authors: Wang
authors: Feng
authors: F
authors: Ni
authors: Qin
authors: Q
authors: Ge
authors: Yanguang
authors: Y
authors: Yang
authors: Guomei
authors: G
authors: Tai
authors: Xinchen
authors: X
authors: Sun
authors: Jing
authors: J
authors: Cai
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D003131:Combined Modality Therapy; D004938:Esophageal Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D011345:Fenofibrate / Q000494:pharmacology*; D005434:Flow Cytometry; D005720:Gamma Rays; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011836:Radiation Tolerance / Q000187:drug effects*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: C497442:HIF1A protein, human; D000960:Hypolipidemic Agents; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D011838:Radiation-Sensitizing Agents; D011345:Fenofibrate