AZD1480, a JAK inhibitor, inhibits cell growth and survival of colorectal cancer via modulating the JAK2/STAT3 signaling pathway | Zendy

Shuwei Wang | Zendy; Jun Hu | Zendy; Qinhao Guo | Zendy; Yan Zhao | Zendy; Cheng Jiejing | Zendy; Dongsheng Zhang | Zendy; Qiang Fei | Zendy; Juan Li | Zendy; Yueming Sun | Zendy

Open Access

AZD1480, a JAK inhibitor, inhibits cell growth and survival of colorectal cancer via modulating the JAK2/STAT3 signaling pathway

Author(s) -

Shuwei Wang,

Jun Hu,

Qinhao Guo,

Yan Zhao,

Cheng Jiejing,

Dongsheng Zhang,

Qiang Fei,

Juan Li,

Yueming Sun

Publication year - 2014

Publication title -

oncology reports

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 1.094

H-Index - 96

eISSN - 1791-2431

pISSN - 1021-335X

DOI - 10.3892/or.2014.3477

Subject(s) - cancer research , janus kinase 2 , janus kinase , oncogene , stat3 , cell cycle , jak stat signaling pathway , signal transduction , cell growth , colorectal cancer , carcinogenesis , pim1 , medicine , apoptosis , phosphorylation , biology , cancer , microbiology and biotechnology , tyrosine kinase , biochemistry , serine

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.

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