Blocking of the EGFR‑STAT3 signaling pathway through afatinib treatment inhibited the intrahepatic cholangiocarcinoma

  • Authors:
    • Changhe Zhang
    • Hong Xu
    • Zhenping Zhou
    • Ye Tian
    • Xiaofei Cao
    • Guochang Cheng
    • Qinghong Liu
  • View Affiliations

  • Published online on: April 5, 2018     https://doi.org/10.3892/etm.2018.6038
  • Pages: 4995-5000
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Abstract

Epidermal growth factor receptor (EGFR) and downstream signal transducer and activator of transcription 3 (STAT3) signaling have been extensively implicated in various human neoplasms. Recently, a novel EGFR inhibitor, known as afatinib, has exhibited broad antitumor activities in a variety of tumors. Therefore, the present study attempted to investigate the impact of this agent on intrahepatic cholangiocarcinoma (ICC). Initially, immunohistochemical assays were performed on 15 human ICC specimens and their adjacent tissues in order to assess the protein levels of phosphorylated EGFR (pEGFR) and pSTAT3. Subsequently, the human ICC cell lines JCK and OZ were exposed to different doses of afatinib, and then cell viability and apoptosis were determined by MTT assay and flow cytometry, respectively. Furthermore, immunoblotting was applied to detect any variations in the phosphorylated protein levels of EGFR and STAT3 in afatinib‑treated ICC cells. The results of the current study demonstrated that ICC specimens had evidently increased pEGFR and pSTAT3 protein levels as compared with the adjacent noncancerous tissues. Further in vitro experiments indicated that afatinib evidently blocked ICC cell growth and induced cell apoptosis. At the protein level, pEGFR and pSTAT3 were evidently attenuated by afatinib‑administration. In conclusion, the present study clearly determined that afatinib exerts an antitumor effect on ICC cells by silencing the EGFR‑STAT3 signaling pathway. This novel agent deserves further investigation as a potential therapeutic strategy for ICC.
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June-2018
Volume 15 Issue 6

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Zhang C, Xu H, Zhou Z, Tian Y, Cao X, Cheng G and Liu Q: Blocking of the EGFR‑STAT3 signaling pathway through afatinib treatment inhibited the intrahepatic cholangiocarcinoma. Exp Ther Med 15: 4995-5000, 2018
APA
Zhang, C., Xu, H., Zhou, Z., Tian, Y., Cao, X., Cheng, G., & Liu, Q. (2018). Blocking of the EGFR‑STAT3 signaling pathway through afatinib treatment inhibited the intrahepatic cholangiocarcinoma. Experimental and Therapeutic Medicine, 15, 4995-5000. https://doi.org/10.3892/etm.2018.6038
MLA
Zhang, C., Xu, H., Zhou, Z., Tian, Y., Cao, X., Cheng, G., Liu, Q."Blocking of the EGFR‑STAT3 signaling pathway through afatinib treatment inhibited the intrahepatic cholangiocarcinoma". Experimental and Therapeutic Medicine 15.6 (2018): 4995-5000.
Chicago
Zhang, C., Xu, H., Zhou, Z., Tian, Y., Cao, X., Cheng, G., Liu, Q."Blocking of the EGFR‑STAT3 signaling pathway through afatinib treatment inhibited the intrahepatic cholangiocarcinoma". Experimental and Therapeutic Medicine 15, no. 6 (2018): 4995-5000. https://doi.org/10.3892/etm.2018.6038