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Erschienen in: Journal of Cancer Research and Clinical Oncology 1/2021

08.09.2020 | Original Article – Cancer Research

Gemcitabine potentiates anti-tumor effect of resveratrol on pancreatic cancer via down-regulation of VEGF-B

verfasst von: Yinan Yang, Wencong Tian, Lei Yang, Qiong Zhang, Mengmeng Zhu, Yuansheng Liu, Jing Li, Liang Yang, Jie Liu, Yanna Shen, Zhi Qi

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 1/2021

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Abstract

Purpose

In our previous study, we discovered that resveratrol (RSV) had potential tumor-promoting effect on pancreatic cancer (PaCa) via up-regulation of VEGF-B. Therefore, we assumed that a pharmacological inhibitor of VEGF-B should potentiate the anti-tumor effect of RSV on PaCa.

Methods

Real-time PCR and western blotting were used to examine VEGF-B mRNA and protein levels. Cell viability and cell apoptosis were assessed by CCK-8 assay and flow cytometry analysis, respectively. PaCa cell-bearing nude mice were used to evaluate the anti-cancer effects of single treatment or co-administration of RSV and gemcitabine (GEM).

Results

We found that treatment with GEM alone dramatically decreased VEGF-B expression in comparison with control group, indicating that GEM is a potential pharmacological inhibitor of VEGF-B in PaCa. The co-administration of RSV and GEM significantly lowered expression of VEGF-B and increased phosphorylation level of GSK3β at Ser9 when compared to RSV alone treatment either in vitro or in vivo. Combination of RSV and GEM significantly increased cell death and apoptosis of PaCa cells in vitro and inhibited tumor growth in vivo in comparison with RSV or GEM alone treatment. Furthermore, we found that the anti-tumor effect in combination group was dramatically weakened after VEGF-B overexpressed in PaCa cells.

Conclusion

These results suggest that VEGF-B signaling pathway plays an important role in the development of PaCa and combination of GEM and RSV would be a promising modality for clinical PaCa therapy.
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Metadaten
Titel
Gemcitabine potentiates anti-tumor effect of resveratrol on pancreatic cancer via down-regulation of VEGF-B
verfasst von
Yinan Yang
Wencong Tian
Lei Yang
Qiong Zhang
Mengmeng Zhu
Yuansheng Liu
Jing Li
Liang Yang
Jie Liu
Yanna Shen
Zhi Qi
Publikationsdatum
08.09.2020
Verlag
Springer Berlin Heidelberg
Erschienen in
Journal of Cancer Research and Clinical Oncology / Ausgabe 1/2021
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-020-03384-7

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