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2018 ; 15
(6
): 4995-5000
Nephropedia Template TP
gab.com Text
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English Wikipedia
Blocking of the EGFR-STAT3 signaling pathway through afatinib treatment inhibited
the intrahepatic cholangiocarcinoma
#MMPMID29805522
Zhang C
; Xu H
; Zhou Z
; Tian Y
; Cao X
; Cheng G
; Liu Q
Exp Ther Med
2018[Jun]; 15
(6
): 4995-5000
PMID29805522
show ga
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.