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2016 ; 7
(51
): 84190-84200
Nephropedia Template TP
gab.com Text
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Metformin potentiates anti-tumor effect of resveratrol on pancreatic cancer by
down-regulation of VEGF-B signaling pathway
#MMPMID27705937
Zhu M
; Zhang Q
; Wang X
; Kang L
; Yang Y
; Liu Y
; Yang L
; Li J
; Yang L
; Liu J
; Li Y
; Zu L
; Shen Y
; Qi Z
Oncotarget
2016[Dec]; 7
(51
): 84190-84200
PMID27705937
show ga
Our previous study showed that resveratrol (RSV) exhibited not only anti-tumor
effect, but also had potential tumor promotion effect on pancreatic cancer (Paca)
cells through up-regulation of VEGF-B. We determined whether metformin (MET)
could potentiate the anti-tumor effect of RSV on PaCa in this study. Combination
of RSV (100 ?mol/l) and MET (20 mmol/l) significantly inhibited tumor growth and
increased apoptosis of human PaCa in comparison with RSV or MET alone treatment
in PaCa cell lines (Miapaca-2, Panc-1 and Capan-2). Combination of RSV (60 mg/kg,
gavage) and MET (250 mg/kg, i.p.) significantly inhibited tumor growth in PaCa
bearing nude mice (subcutaneous injection of 5 × 106 Miapaca-2 cells) in
comparison with RSV or MET alone treatment on day 40. Combination treatment
significantly decreased VEGF-B expression and inhibited activity of GSK-3? when
compared to the RSV alone treatment. Up-regulated expressions of Bax, cleaved
caspase-3 and down-regulated expression of Bcl-2 were observed in RSV+ MET group
in comparison with RSV group either in vitro or in vivo. Inhibition of VEGF-B by
VEGF-B small interfering RNA (siRNA) mimicked the effects of MET on PaCa cells.
These results suggested that MET, a potential pharmacological inhibitor of VEGF-B
signaling pathway, potentiated the anti-tumor effect of RSV on PaCa, and
combination of MET and RSV would be a promising modality for clinical PaCa
therapy.