Deng Fengliu, Ouyang Mingwen, Wang Xiaofei, Yao Xueqing, Chen Yeming, Tao Tao, Sun Xuegang, Xu Lijun, Tang Jing, Zhao Liang
Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China.
Oncotarget. 2016 Nov 22;7(47):77087-77095. doi: 10.18632/oncotarget.12800.
Anesthetics are unavoidable to colorectal cancer (CRC) patients who underwent surgical treatment. Thus, the molecular mechanisms underlying the role of the intravenous anesthetics in CRC metastasis are still unclear. In this study, the effects of intravenous anesthetics, such as propofol, etomidate and dexmedetomidine, on cell migration were determined. The migration of CRC cells was inhibited by propofol in vitro, but not in vivo. Etomidate, however, promoted the migration of CRC cells both in vitro and in vivo. Epithelial-mesenchymal transition (EMT) mediated the promotive effect of propofol and etomidate on the migration of CRC cells through PI3K/AKT signaling pathway. Dexmedetomidine alone or in combination with propofol or etomidate had minor effect on the migration of CRC cells. These findings indicate that propofol inhibites CRC cell migration in vitro. Etomidate playes a role for prompting CRC metastasis progression by activating (PI3K)/AKT signaling and inducing EMT. It provides an important hint for the clinical application of these anesthetics.
麻醉药对于接受手术治疗的结直肠癌(CRC)患者来说是不可避免的。因此,静脉麻醉药在CRC转移中作用的分子机制仍不清楚。在本研究中,确定了静脉麻醉药如丙泊酚、依托咪酯和右美托咪定对细胞迁移的影响。丙泊酚在体外抑制CRC细胞迁移,但在体内无此作用。然而,依托咪酯在体外和体内均促进CRC细胞迁移。上皮-间质转化(EMT)通过PI3K/AKT信号通路介导丙泊酚和依托咪酯对CRC细胞迁移的促进作用。单独使用右美托咪定或与丙泊酚或依托咪酯联合使用对CRC细胞迁移影响较小。这些发现表明丙泊酚在体外抑制CRC细胞迁移。依托咪酯通过激活(PI3K)/AKT信号并诱导EMT促进CRC转移进展。这为这些麻醉药的临床应用提供了重要提示。