Resveratrol plays dual roles in pancreatic cancer cells
Although the potential anticancer effect of resveratrol (RSV) on pancreatic cancer has been reported, its mechanism was not fully understood. The role of vascular endothelial growth factor B (VEGF-B) in cancer remains controversial. Herein, we aimed to examine whether the anticancer effect of RSV was related to the VEGF-B.
The effect of RSV on pancreatic cancer cell line (capan-2 cells) was evaluated by CCK-8 assay, Hoechst 33342 staining, and flow cytometry. The mRNA level of VEGF-B was measured by real-time PCR. VEGF-B expression was knockdown by small interfering RNA (siRNA).The protein levels of VEGF-B, glycogen synthase kinase-3 beta (GSK-3β), and Bax were measured by Western blot.
Resveratrol treatment inhibited tumor growth, induced apoptosis, and up-regulated Bax expression in capan-2 cells. The mRNA and protein levels of VEGF-B were up-regulated after RSV treatment. However, VEGF-B siRNA treatment increased the apoptotic rate, and inhibited tumor activator GSK-3β, while Bax expression was not affected. The combination of RSV and VEGF-B siRNA showed significantly higher apoptotic rate in comparison with RSV or VEGF-B siRNA mono-treatment group.
Resveratrol plays dual roles in pancreatic cancer: as a tumor suppressor via the up-regulation of Bax; as a tumor activator via the up-regulation of VEGF-B; and the anticancer effect of RSV is much stronger than the cancer promotion effect. The combination of RSV with pharmacological inhibitor of VEGF-B might, therefore, be a promising modality for clinical pancreatic cancer therapy.
KeywordsResveratrol VEGF-B Tumor apoptosis Pancreatic cancer
This research was supported by the National Natural Science Foundation of China (No. 81201206), the Natural Science Foundation of Tianjin (No. 11JCYBJC10000), the Research Fund for the Doctoral Program of Ministry of Education of China (No. 20120031120058), the National Natural Science Foundation of China (No. 81101222), and Science Foundation of Tianjin Medical University (No. 2010ky16). The authors thank Pro. Yang Wang, Zhiping Xie for providing us instruments, and also thank Ms. Nancy Bai for the careful language correction.
Conflict of interest
We declare that we have no conflict of interest.
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