Sevoflurane inhibits the migration and invasion of colorectal cancer cells through regulating ERK/MMP-9 pathway by up-regulating miR-203
Sevoflurane inhibits the migration and invasion of colorectal cancer cells through regulating ERK/MMP-9 pathway by up-regulating miR-203
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DOI：
10.1016/j.ejphar.2019.01.025
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发表时间：
2019-05-05
影响因子：
5
通讯作者：
Han, Xin
中科院分区：
文献类型：
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作者：
Fan, Lihua;Wu, Yini;Han, Xin
手术切除是有肿瘤扩散和转移风险的结直肠癌（CRC）患者的主要治疗方法。七氟醚是一种吸入麻醉，可调节各种癌症的迁移和侵袭。然而，七氟醚对结直肠癌细胞的影响及其机制尚不清楚。本实验采用不同浓度的七氟醚体外处理SW620和HCT116细胞6 h。我们通过3-（4,5-二甲基-2-噻唑基）-2,5-二苯基-2- h -溴化四氮唑或跨孔法测定了七氟醚对细胞存活、迁移和侵袭的影响。此外，我们探索了七氟烷与miR-203和Roundabout1 （Robo1）以及细胞外信号调节激酶（ERK）和基质金属蛋白酶-9 （MMP-9）途径的相互作用。结果表明，七氟醚对SW620和HCT116细胞的迁移和侵袭具有浓度依赖性。此外，不同浓度的七氟醚抑制ERK的磷酸化。miR-203的表达受损，而七氟醚逆转了CRC细胞中miR-203的表达。此外，抑制miR-203减弱了七氟醚对细胞迁移、侵袭和磷酸化ERK水平的抑制作用。值得注意的是，作为ERK的下游，MMP-9参与了CRC细胞中七氟醚介导的过程。此外，Robo1被认为是miR-203的靶点，并被七氟烷处理抑制。这些结果表明，七氟醚通过miR-203/Robo1调控结直肠癌细胞中ERK/MMP-9通路，抑制细胞迁移和侵袭，这对于麻醉剂预防结直肠癌转移具有重要的临床意义。
Surgery resection is the primary treatment for colorectal cancer (CRC) patients with the risk of cancer dissemination and metastasis. Sevoflurane is one inhalational anesthesia which regulates migration and invasion in varying cancers. However, the effect of sevoflurane on CRC cells and its mechanism remain poorly understood. In this study, SW620 and HCT116 cells were treated with different concentrations of sevoflurane for 6 h in vitro. We measured the effect of sevoflurane on cell survival, migration and invasion by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide or trans-well assays. Moreover, we explored the interaction between sevoflurane and miR-203 and Roundabout1 (Robo1) as well as the extracellular signal-regulated kinase (ERK) and matrix metalloproteinase-9 (MMP-9) pathway. Results showed that sevoflurane inhibited cell migration and invasion in SW620 and HCT116 cells in a concentration dependent manner. Moreover, different concentrations of sevoflurane suppressed the phosphorylation of ERK. miR-203 expression was impaired while sevoflurane reversed the expression of miR-203 in CRC cells. In addition, inhibition of miR-203 attenuated the inhibitory effect of sevoflurane on cell migration, invasion and phosphorylated ERK level. Notably, MMP-9, as a downstream of ERK, was involved in sevoflurane-mediated processes in CRC cells. Besides, Robo1 was indicated as a target of miR-203 and inhibited by sevoflurane treatment. These results indicated that sevoflurane suppressed cell migration and invasion through regulating ERK/MMP-9 pathway via miR-203/Robo1 in CRC cells, indicating important clinical implications for anesthetic agents to prevent metastasis in CRC.