JAK2 inhibitor blocks the inflammation and growth of esophageal squamous cell carcinoma in vitro through the JAK/STAT3 pathway

  • Authors:
    • Juemin Fang
    • Li Chu
    • Chunyan Li
    • Yijing Chen
    • Fei Hu
    • Xi Zhang
    • Huaxin Zhao
    • Zhuqing Liu
    • Qing Xu
  • View Affiliations

  • Published online on: November 14, 2014     https://doi.org/10.3892/or.2014.3609
  • Pages: 494-502
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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.
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January-2015
Volume 33 Issue 1

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Fang J, Chu L, Li C, Chen Y, Hu F, Zhang X, Zhao H, Liu Z and Xu Q: JAK2 inhibitor blocks the inflammation and growth of esophageal squamous cell carcinoma in vitro through the JAK/STAT3 pathway. Oncol Rep 33: 494-502, 2015.
APA
Fang, J., Chu, L., Li, C., Chen, Y., Hu, F., Zhang, X. ... Xu, Q. (2015). JAK2 inhibitor blocks the inflammation and growth of esophageal squamous cell carcinoma in vitro through the JAK/STAT3 pathway. Oncology Reports, 33, 494-502. https://doi.org/10.3892/or.2014.3609
MLA
Fang, J., Chu, L., Li, C., Chen, Y., Hu, F., Zhang, X., Zhao, H., Liu, Z., Xu, Q."JAK2 inhibitor blocks the inflammation and growth of esophageal squamous cell carcinoma in vitro through the JAK/STAT3 pathway". Oncology Reports 33.1 (2015): 494-502.
Chicago
Fang, J., Chu, L., Li, C., Chen, Y., Hu, F., Zhang, X., Zhao, H., Liu, Z., Xu, Q."JAK2 inhibitor blocks the inflammation and growth of esophageal squamous cell carcinoma in vitro through the JAK/STAT3 pathway". Oncology Reports 33, no. 1 (2015): 494-502. https://doi.org/10.3892/or.2014.3609