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2018 ; 24
(ä): 4046-4053
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Cervical Cancer Cell Growth, Drug Resistance, and Epithelial-Mesenchymal
Transition Are Suppressed by y-Secretase Inhibitor RO4929097
#MMPMID29899322
Wang L
; Dai G
; Yang J
; Wu W
; Zhang W
Med Sci Monit
2018[Jun]; 24
(ä): 4046-4053
PMID29899322
show ga
BACKGROUND The Notch signaling pathway has been reported to play a pivotal role
in tumorigenesis. Emerging evidence has demonstrated that the Notch signaling
pathway regulates several cellular processes. The present study investigated the
effect of the Notch signaling pathway on cell growth, invasiveness, and drug
resistance, as well as epithelial-mesenchymal transition (EMT), of cervical
cancer cells. MATERIAL AND METHODS We used quantitative real-time polymerase
chain reaction (qRT-PCR) and Western blot analysis to measure the expression
level of Notch2. CCK-8, clonality, wound healing, and Transwell assays were used
to evaluate the effect of ?-secretase inhibitor (GSI) RO4929097 on cervical
cancer cell lines HeLa and Caski. To explore the role of the Notch signaling
pathway in EMT, the epithelial and mesenchymal markers were detected by qRT-PCR
and Western blot after cervical cancer cell lines were treated with GSI
RO4929097. RESULTS The expression of Notch2 was found to increase in cervical
cancer cell lines compared with the normal immortalized human cervical epithelial
cells. GSI RO4929097 was confirmed to inhibit the Notch signaling pathway and
impaired the proliferation, drug resistance, migration, and invasion abilities of
cervical cancer cells. The protein expression levels of the mesenchymal
biomarkers Snail, Twist, and neural cadherin (N-cadherin) decreased; however, the
expression of the epithelial biomarker epithelial cadherin (E-cadherin) increased
in the cervical cancer cells treated with GSI RO4929097. CONCLUSIONS Notch
signaling pathway plays an important role in the development and progression of
cervical cancer. Blockade of the Notch pathway using GSI RO4929097 inhibited cell
growth and reduced chemoresistance, invasion, metastasis, and EMT in cervical
cancer cells.
|Amyloid Precursor Protein Secretases/antagonists & inhibitors/*metabolism
[MESH]
|Benzazepines/*pharmacology/therapeutic use
[MESH]