Authors: Lei Yang Liang Yang Wencong Tian Jing Li Jie Liu Mengmeng Zhu Yan Zhang Yinan Yang Fei Liu Qiong Zhang Qianqian Liu Yanna Shen Zhi Qi
Publish Date: 2014/03/07
Volume: 140, Issue: 5, Pages: 749-755
Abstract
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 VEGFB in cancer remains controversial Herein we aimed to examine whether the anticancer effect of RSV was related to the VEGFBThe effect of RSV on pancreatic cancer cell line capan2 cells was evaluated by CCK8 assay Hoechst 33342 staining and flow cytometry The mRNA level of VEGFB was measured by realtime PCR VEGFB expression was knockdown by small interfering RNA siRNAThe protein levels of VEGFB glycogen synthase kinase3 beta GSK3β and Bax were measured by Western blotResveratrol treatment inhibited tumor growth induced apoptosis and upregulated Bax expression in capan2 cells The mRNA and protein levels of VEGFB were upregulated after RSV treatment However VEGFB siRNA treatment increased the apoptotic rate and inhibited tumor activator GSK3β while Bax expression was not affected The combination of RSV and VEGFB siRNA showed significantly higher apoptotic rate in comparison with RSV or VEGFB siRNA monotreatment groupResveratrol plays dual roles in pancreatic cancer as a tumor suppressor via the upregulation of Bax as a tumor activator via the upregulation of VEGFB and the anticancer effect of RSV is much stronger than the cancer promotion effect The combination of RSV with pharmacological inhibitor of VEGFB might therefore be a promising modality for clinical pancreatic cancer therapyThis 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
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