title: JAK2 inhibitor blocks the inflammation and growth of esophageal squamous cell carcinoma in vitro through the JAK/STAT3 pathway.
abstract: Recent research indicates that the Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) pathway may play an important role in chronic inflammation which promotes cancer progression, yet the mechanism is not clear. The present study aimed to investigate the role of the JAK/STAT3 pathway in the growth and cancer-related inflammation (CRI) of esophageal squamous cell carcinoma (ESCC) by studying the crosstalk between the JAK/STAT3 pathway and nuclear factor-κB (NF-κB) and cyclooxygenase-2 (COX-2) which are important inflammatory factors associated with tumorigenesis. Cell growth and the cell cycle were assessed by CCK-8 assays and flow cytometry, respectively. The protein levels of STAT3, phosphorylated STAT3, VEGF, NF-κB p65, phosphorylated NF-κB p65 and COX-2 in ESCC cells following treatment with JAK2 inhibitor for 48 h or interleukin-6 (IL-6) for 24 h were detected. RT-PCR was performed to study the interaction among STAT3, NF-κB and COX-2 by transfection of siRNAs targeted at STAT3 and NF-κB. STAT3 was activated in 3 ESCC cell lines at different levels. Blocking the JAK/STAT3 pathway inhibited cancer growth through regulation of cell growth, cell cycle and angiogenesis. Likewise, abrogation of the JAK/STAT3 pathway decreased CRI by downregulating levels of NF-κB p65 phosphorylation, COX-2 and IL-6 concentration. In addition, CRI and cancer growth were accelerated by IL-6 through stimulation of the JAK/STAT3 and NF-κB p65 pathway. Moreover, STAT3 and NF-κB both regulated COX-2 as a downstream gene. The JAK/STAT3 pathway is an important pathway which links CRI and cancer growth through IL-6 and crosstalk with the NF-κB p65 subunit and COX-2. The STAT3 pathway could be a novel target both for cancer treatment and prevention in ESCC.
authors.affiliation: Department of Medical Oncology, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai 200072, P.R. China.
authors.forename: Juemin
authors.initials: J
authors.lastname: Fang
authors.affiliation: Department of Medical Oncology, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai 200072, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Chu
authors.affiliation: Department of Medical Oncology, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai 200072, P.R. China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Medical Oncology, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai 200072, P.R. China.
authors.forename: Yijing
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Medical Oncology, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai 200072, P.R. China.
authors.forename: Fei
authors.initials: F
authors.lastname: Hu
authors.affiliation: Department of Medical Oncology, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai 200072, P.R. China.
authors.forename: Xi
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Medical Oncology, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai 200072, P.R. China.
authors.forename: Huaxin
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Medical Oncology, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai 200072, P.R. China.
authors.forename: Zhuqing
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Medical Oncology, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai 200072, P.R. China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Xu
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004938:Esophageal Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000209:etiology; D015850:Interleukin-6 / Q000378:metabolism / Q000494:pharmacology; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D020032:Tyrphostins / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D015850:Interleukin-6; D016328:NF-kappa B; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; C507924:JAK2 protein, human; D053614:Janus Kinase 2