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2015 ; 6
(12
): 9999-10015
Nephropedia Template TP
gab.com Text
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English Wikipedia
Aspirin counteracts cancer stem cell features, desmoplasia and gemcitabine
resistance in pancreatic cancer
#MMPMID25846752
Zhang Y
; Liu L
; Fan P
; Bauer N
; Gladkich J
; Ryschich E
; Bazhin AV
; Giese NA
; Strobel O
; Hackert T
; Hinz U
; Gross W
; Fortunato F
; Herr I
Oncotarget
2015[Apr]; 6
(12
): 9999-10015
PMID25846752
show ga
Pancreatic ductal adenocarcinoma (PDA) is characterized by an extremely poor
prognosis. An inflammatory microenvironment triggers the pronounced desmoplasia,
the selection of cancer stem-like cells (CSCs) and therapy resistance. The
anti-inflammatory drug aspirin is suggested to lower the risk for PDA and to
improve the treatment, although available results are conflicting and the effect
of aspirin to CSC characteristics and desmoplasia in PDA has not yet been
investigated. We characterized the influence of aspirin on CSC features, stromal
reactions and gemcitabine resistance. Four established and 3 primary PDA cell
lines, non-malignant cells, 3 patient tumor-derived CSC-enriched spheroidal
cultures and tissues from patients who did or did not receive aspirin before
surgery were analyzed using MTT assays, flow cytometry, colony and spheroid
formation assays, Western blot analysis, antibody protein arrays, electrophoretic
mobility shift assays (EMSAs), immunohistochemistry and in vivo
xenotransplantation. Aspirin significantly induced apoptosis and reduced the
viability, self-renewal potential, and expression of proteins involved in
inflammation and stem cell signaling. Aspirin also reduced the growth and
invasion of tumors in vivo, and it significantly prolonged the survival of mice
with orthotopic pancreatic xenografts in combination with gemcitabine. This was
associated with a decreased expression of markers for progression, inflammation
and desmoplasia. These findings were confirmed in tissue samples obtained from
patients who had or had not taken aspirin before surgery. Importantly, aspirin
sensitized cells that were resistant to gemcitabine and thereby enhanced the
therapeutic efficacy. Aspirin showed no obvious toxic effects on normal cells,
chick embryos or mice. These results highlight aspirin as an effective,
inexpensive and well-tolerated co-treatment to target inflammation, desmoplasia
and CSC features PDA.