Propofol attenuates pancreatic cancer malignant potential via inhibition of NMDA receptor

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• 作者：Xiangyuan Chen^a ; ^b ; ^c ; ¹ ; Qichao Wu^a ; ^b ; ^c ; ¹ ; Li You^a ; ^b ; ¹ ; Sisi Chen^d ; Minmin Zhu^a ; ^b ; ^{zhu_mm@126.com} ; Changhong Miao^a ; ^b ; ^{miao_chh@126.com}
• 关键词：Propofol ; CaMK II ; HIF-1α ; VEGF ; NMDA
• 刊名：European Journal of Pharmacology
• 出版年：2017
• 出版时间：15 January 2017
• 年：2017
• 卷：795
• 期：Complete
• 页码：150-159
• 全文大小：2362 K
• 卷排序：795

文摘

Propofol is a commonly used intravenous anesthetic, and could attenuate cancer cells malignant potential via inhibiting hypoxia-inducible factor-1α (HIF-1α) expression. However, the mechanism is still inclusive. In the present study, we mainly focus on the mechanism by which propofol down-regulated HIF-1α expression and malignant potential in pancreatic cancer cells. Human pancreatic cancer cells (Miapaca-2 and Panc-1) in vitro and murine pancreatic cancer cell (Panc02) in vivo were used to assess the effect of propofol on vascular endothelial growth factor (VEGF) expression and migration of pancreatic cancer cells. Propofol inhibited cells migration, expression of VEGF and HIF-1α, phosphorylation of extracellular regulated protein kinases (ERK), AKT, Ca2+/calmodulin dependent protein kinases II (CaMK II), and Ca2+ concentration in a concentration-dependent manner (5, 25, 50, 100 μM). Furthermore, MK801, an inhibitor of NMDA receptor, and KN93, an inhibitor of CaMK II, could inhibit the expression of VEGF, HIF-1a, p-AKT, p-ERK, p-CaMK II in vitro, growth of tumor and VEGF expression in vivo, which were similar to the effect of propofol. In addition, the anti-tumor effect of propofol could be counteracted by rapastinel, an activator of NMDA receptor. Our study indicated that propofol suppressed VEGF expression and migration ability of pancreatic cancer cells in vitro and in vivo, probably via inhibiting NMDA receptor.