Resveratrol plays dual roles in pancreatic cancer cells

Yang, Lei; Yang, Liang; Tian, Wencong; Li, Jing; Liu, Jie; Zhu, Mengmeng; Zhang, Yan; Yang, Yinan; Liu, Fei; Zhang, Qiong; Liu, Qianqian; Shen, Yanna; Qi, Zhi

doi:10.1007/s00432-014-1624-4

Cited by 39 publications

(38 citation statements)

References 36 publications

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“…Total RNA was isolated from equal number of islets using Trizol reagent (Takara Bio, Inc.) as described previously [20]. In brief, for cDNA synthesis 1.0 lg RNA was used, and reactions were carried out using the reverse transcription system (Promega, Shanghai).…”

Section: Quantitative Real-time Pcr (Qpcr)mentioning

confidence: 99%

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Optimal method for short-term or long-term islet preservation: comparison of islet culture, cold preservation and cryopreservation

et al. 2014

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Islet preservation plays an important role for the success of islet transplantation. To determine the optimal method for islet preservation, we compared the outcomes of islet culture, cold preservation, and cryopreservation in this study. Isolated rat islets were divided into three groups: 37 °C group (conventional culture at 37 °C in RPMI-1640 medium), 4 °C group (cold preservation at 4 °C in University of Wisconsin (UW) solution), and -80 °C group (cryopreservation at -80 °C with dimethyl sulfoxide (DMSO)). Recovery rate, Calcein-AM/PI double staining, insulin release, mRNA level of hypoxia-inducible factor-1α (HIF-1α), and protein level of Bax in islets were examined after short-term (1 day) or long-term (7 days) preservation. After either short-term or long-term preservation, 4 °C group showed higher recovery rate of the islets number, lower percentage of PI positive area, better insulin release ability, and lower expression levels of HIF-1α and Bax in comparison to the 37 or -80 °C group. Meanwhile, islets in 37 °C group showed better function, and down-regulation of HIF-1α and Bax than those in -80 °C group on day 1; however, worse function of islets, up-regulated HIF-1α and Bax in 37 °C group were observed in comparison to -80 °C group on day 7. These results suggest that cold preservation at 4 °C in UW solution is the optimal method in comparison to the conventional culture at 37 °C or cryopreservation at -80 °C for short-term or long-term islet preservation. Furthermore, the potential mechanism may relate to, at least in part, apoptosis induced by the HIF-1α.

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Section: Quantitative Real-time Pcr (Qpcr)mentioning

confidence: 99%

“…Western blot analysis was performed as described previously [20]. In brief, cells were lysed and incubated for 30 min in ice-cold RIPA buffer.…”

Section: Western Blot Analysismentioning

confidence: 99%

Optimal method for short-term or long-term islet preservation: comparison of islet culture, cold preservation and cryopreservation

et al. 2014

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“…Furthermore, we examined the protein level of GSK-3β, which has been reported as a down-stream molecule of VEGF-B in our previous study [21]. GSK-3β served as a tumor activator in pancreatic cancer, and phosphorylation at Ser 9 reduced the activity of this kinase [26].…”

Section: Resultsmentioning

confidence: 99%

“…RSV is shown to prevent a variety of cancers; including hepatocellular carcinoma [15], non-small cell lung adenocarcinoma [16], oral carcinoma [17], osteosarcomas [18], as well as PaCa [19, 20]. Interestingly, in previous study, we found that RSV played dual roles in PaCa cells, namely as a tumor suppressor via the promotion of apoptosis; as a tumor activator via the up-regulation of VEGF-B; and the anti-cancer effect of RSV was much stronger than the cancer promotion effect [21]. Therefore, we assumed that combination of RSV with pharmacological inhibitor of VEGF-B signaling pathway could potentiate the anti-tumor effect of RSV, and would be a promising modality for clinical PaCa therapy.…”

Section: Introductionmentioning

confidence: 99%

Metformin potentiates anti-tumor effect of resveratrol on pancreatic cancer by down-regulation of VEGF-B signaling pathway

et al. 2016

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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 μmol/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-3β 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.

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“…Resveratrol has a dual role in pancreatic cancer cells: on one hand, it acts as a tumor suppressor by accelerating apoptosis; on the other hand, it promotes tumorigenesis by up-regulating the expression of VEGF-B, which then activates GSK-3β and inhibits apoptosis [20]. Metformin suppresses resveratrol-induced expression of VEGF-B, thereby potentiating the anti-cancer effect of resveratrol via inhibition of VEGF-B/GSK-3β signaling pathway [19].…”

Section: Classic Anti-cancer Mechanisms Of Metforminmentioning

confidence: 99%

Anti-tumor activity of metformin: from metabolic and epigenetic perspectives

Mao

Zhai

et al. 2016

Oncotarget

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Metformin has been used to treat type 2 diabetes for over 50 years. Epidemiological, preclinical and clinical studies suggest that metformin treatment reduces cancer incidence in diabetes patients. Due to its potential as an anti-cancer agent and its low cost, metformin has gained intense research interest. Its traditional anti-cancer mechanisms involve both indirect and direct insulin-dependent pathways. Here, we discussed the anti-tumor mechanism of metformin from the aspects of cell metabolism and epigenetic modifications. The effects of metformin on anti-cancer immunity and apoptosis were also described. Understanding these mechanisms will shed lights on application of metformin in clinical trials and development of anti-cancer therapy.

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Resveratrol plays dual roles in pancreatic cancer cells

Cited by 39 publications

References 36 publications

Optimal method for short-term or long-term islet preservation: comparison of islet culture, cold preservation and cryopreservation

Optimal method for short-term or long-term islet preservation: comparison of islet culture, cold preservation and cryopreservation

Metformin potentiates anti-tumor effect of resveratrol on pancreatic cancer by down-regulation of VEGF-B signaling pathway

Anti-tumor activity of metformin: from metabolic and epigenetic perspectives

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