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2017 ; 13
(4
): 2260-2268
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Notch signaling is important for epithelial-mesenchymal transition induced by low
concentrations of doxorubicin in osteosarcoma cell lines
#MMPMID28454389
Yang J
; Guo W
; Wang L
; Yu L
; Mei H
; Fang S
; Chen A
; Liu Y
; Xia K
; Liu G
Oncol Lett
2017[Apr]; 13
(4
): 2260-2268
PMID28454389
show ga
Osteosarcoma is an aggressive pediatric tumor affecting growing bones that
typically occurs in adolescents and young adults. Although advances in treatment
have been made in recent years, a high proportion of patients relapse due to
metastases, which are frequently resistant to chemotherapy and pose a significant
threat to long-term survival. Previous studies have demonstrated that the
epithelial-mesenchymal transition (EMT) is associated with cancer occurrence and
metastasis, and our previous study demonstrated the occurrence of EMT in
osteosarcoma. Notch is a regulator involved in several cellular processes, and
previous studies have identified that the Notch signaling pathway may be
activated during chemotherapy. However, whether chemotherapy affects the EMT
remains to be elucidated. To address this issue, in the present study
osteosarcoma cells were exposed to sublethal doses of doxorubicin, which resulted
in upregulation of the expression of genes in the Notch signaling pathway and its
target genes. Furthermore, doxorubicin treatment promoted mesenchymal-like
properties and enhanced the migration and invasion of cells. In addition,
treatment with the selective ?-secretase inhibitor DAPT was able to prevent the
EMT and inhibit the in vitro migration of osteosarcoma cells. The results of this
study suggested that there is a significant correlation between the Notch
signaling pathway and the EMT, and revealed an underlying molecular mechanism by
which doxorubicin may induce the EMT via Notch signaling.