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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Am+J+Cancer+Res
2017 ; 7
(7
): 1486-1500
Nephropedia Template TP
gab.com Text
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English Wikipedia
The addition of calcitriol or its synthetic analog EB1089 to lapatinib and
neratinib treatment inhibits cell growth and promotes apoptosis in breast cancer
cells
#MMPMID28744399
Segovia-Mendoza M
; Díaz L
; Prado-Garcia H
; Reginato MJ
; Larrea F
; García-Becerra R
Am J Cancer Res
2017[]; 7
(7
): 1486-1500
PMID28744399
show ga
In breast cancer the use of small molecule inhibitors of tyrosine kinase activity
of the ERBB family members improves survival thus represents a valuable
therapeutic strategy. The addition of calcitriol, the most active metabolite of
vitamin D, or some of its analogs, to conventional anticancer drugs, including
tyrosine kinase inhibitors (TKIs), has shown an increased effect on the
inhibition of cancer cell growth. In this work, we have evaluated the effects and
the mechanism of action of the combination of calcitriol or its analog EB1089
with lapatinib or neratinib on EGFR and/or HER2 positive breast cancer cell
lines. Lapatinib, neratinib, calcitriol and EB1089 inhibited breast cancer cell
proliferation in a concentration-dependent manner. Addition of calcitriol or
EB1089 to TKIs treatment induced more effective inhibiting effect on cell growth
and AKT and MAPK phosphorylation than all compounds alone. The combined
treatments incremented also the expression of active caspase 3 and induced cell
death in two and three-dimensional cell culture and significantly inhibited
anchorage-independent colony formation. Our results suggest that the addition of
calcitriol or its analog EB1089 to conventional targeted therapies, including
lapatinib or neratinib might be of benefit to patients with breast cancer,
particularly those with an EGFR and/or HER2 positive phenotype.