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In the present study, we investigated the association of FOXM1 expression and chemoresistance in pancreatic cancer. Elevated FOXM1 protein levels were associated with gemcitabine chemoresistance in patients with pancreatic cancer. In gemcitabine resistance cell line models of pancreatic cancer, FOXM1 expression increased, which induced gemcitabine chemoresistance in vitro. In pancreatic cancer cells treated with gemcitabine, FOXM1 affected nuclear factor \u03baB (NF-\u03baB) signaling activity. Immunohistochemical analysis demonstrated a negative association of FOXM1 expression and the level of phosphorylated signal transducer and activator of transcription 1 (pSTAT1) in human pancreatic cancer tissues. Dual-luciferase reporter assays and chromatin-immunoprecipitation assays demonstrated that pSTAT1 directly binds to the FOXM1 promoter to down-regulate its transcription. Interferon \u03b3 (IFN\u03b3) promoted gemcitabine-induced cell apoptosis and inhibited cell proliferation in vitro and in vivo by FOXM1 inhibition. These data suggested that FOXM1 enhances chemoresistance to gemcitabine in pancreatic cancer. IFN\u03b3 could be used to down-regulate the expression of FOXM1 through STAT1 phosphorylation, thereby increasing the sensitivity of pancreatic cancer cells to gemcitabine. These studies suggested the sensitization by IFN\u03b3 in pancreatic ductal adenocarcinoma (PDAC) chemotherapy, which requires further clinical studies.<\/jats:p>","DOI":"10.1042\/cs20180816","type":"journal-article","created":{"date-parts":[[2019,2,19]],"date-time":"2019-02-19T16:45:45Z","timestamp":1550594745000},"page":"645-663","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["STAT1-mediated inhibition of FOXM1 enhances gemcitabine sensitivity in pancreatic cancer"],"prefix":"10.1042","volume":"133","author":[{"given":"Chao","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, No. 150, Haping Road, Nangang District, Harbin 150001, China"},{"name":"Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, No.194, Xuefu Road, Nangang District, Harbin 150000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqi","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, No. 150, Haping Road, Nangang District, Harbin 150001, China"},{"name":"Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, No.194, Xuefu Road, Nangang District, Harbin 150000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingwei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, No. 150, Haping Road, Nangang District, Harbin 150001, China"},{"name":"Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, No.194, Xuefu Road, Nangang District, Harbin 150000, 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