title: AZD1480, a JAK inhibitor, inhibits cell growth and survival of colorectal cancer via modulating the JAK2/STAT3 signaling pathway.
abstract: Interleukin (IL)-6 and the downstream Janus kinase (JAK)/signal activator of transcription (STAT) pathway have been found to be important in the development of colorectal cancer (CRC). To develop novel therapies for CRC, we have explored the effects of a novel small-molecule JAK inhibitor (AZD1480) on IL-6/JAK/STAT3 pathway and its potential antitumor activity on the human CRC cell lines (HCT116, HT29 and SW480). The results showed that, AZD1480 effectively prevents constitutive and IL-6-induced JAK2 and STAT-3 phosphorylation and exerted antitumor functional effects by a decrease in proliferation and an increase in apoptosis in CRC cells. The inhibition of tumorigenesis was consistent with the decreased phosphorylated JAK2 and phosphorylated STAT3, and the decreased expression of STAT3‑targeted genes c-Myc, cyclin D2 and IL-6. Thus, AZD1480 is a potential new clinical therapeutic agent for patients with CRC.
authors.affiliation: Department of Colorectal Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Shu-Wei
authors.initials: SW
authors.lastname: Wang
authors.affiliation: Department of Colorectal Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Colorectal Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Qin-Hao
authors.initials: QH
authors.lastname: Guo
authors.affiliation: Department of Colorectal Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Colorectal Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Jie-Jing
authors.initials: JJ
authors.lastname: Cheng
authors.affiliation: Department of Colorectal Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Dong-Sheng
authors.initials: DS
authors.lastname: Zhang
authors.affiliation: Department of Colorectal Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Fei
authors.affiliation: Department of Colorectal Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Colorectal Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Yue-Ming
authors.initials: YM
authors.lastname: Sun
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D019073:HT29 Cells; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors*; D010766:Phosphorylation; D011720:Pyrazoles / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: C545606:AZD 1480; C508600:IL6 protein, human; D015850:Interleukin-6; D011720:Pyrazoles; D011743:Pyrimidines; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C507924:JAK2 protein, human; D053614:Janus Kinase 2