Resveratrol plays dual roles in pancreatic cancer cells
Resveratrol plays dual roles in pancreatic cancer cells
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白藜芦醇在胰腺癌细胞中发挥双重作用
DOI：
10.1007/s00432-014-1624-4
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发表时间：
2014-05-01
影响因子：
3.6
通讯作者：
Qi, Zhi
中科院分区：
文献类型：
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作者：
Yang, Lei;Yang, Liang;Qi, Zhi
白藜芦醇(RSV)对胰腺癌的潜在抗癌作用已有报道，但其作用机制尚不完全清楚。血管内皮生长因子B(VEGF-B)在肿瘤中的作用仍存在争议。方法采用CCK-8比色法、Hoechst 33342染色和流式细胞仪检测RSV对人胰腺癌细胞株CAPAN-2的作用。实时定量聚合酶链式反应检测血管内皮细胞生长因子-B的mRNA水平。结果白藜芦醇可抑制CAPAN-2细胞的生长，诱导细胞凋亡，上调BAX的表达。结果白藜芦醇可抑制CAPAN-2细胞的生长，诱导细胞凋亡，上调β的表达。RSV治疗后，血管内皮生长因子-B的mRNA和蛋白水平均上调。而血管内皮细胞生长因子BsiRNA处理组细胞凋亡率增加，肿瘤激活剂GSK-3β表达受抑，bax表达无明显变化。结论白藜芦醇在胰腺癌中具有双重作用：白藜芦醇通过上调Bax基因的表达而发挥肿瘤抑制作用；通过上调血管内皮生长因子B基因的表达而激活肿瘤细胞；RSV的抗癌作用远强于促癌作用。因此，RSV联合药物抑制剂VEGF-B有望成为临床胰腺癌治疗的一种有前景的方法。
PurposeAlthough 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.MethodsThe 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.ResultsResveratrol 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.ConclusionsResveratrol 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.