Department of Anesthesiology, Wuhan Central Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Anticancer Drugs. 2021 Jun 1;32(5):537-547. doi: 10.1097/CAD.0000000000001061.
Colorectal cancer (CRC) is a common malignancy. Sevoflurane has been reported to involve in the progression in several cancers. However, the molecular mechanism of sevoflurane in CRC progression remains unclear. Quantitative real-time PCR and western blot was used to detect the expression of miR-637 and WNT1. Cell migration, invasion and apoptosis were detected by transwell assay, flow cytometry or western blot, respectively. The interaction between WNT1 and miR-637 was confirmed by luciferase reporter assay, RNA immunoprecipitation assay and pull-down assay. We found sevoflurane could inhibit cell migration and invasion but induced apoptosis in CRC. Besides, the miR-637 level was decreased in CRC tissues and cells but could be rescued by sevoflurane. MiR-637 overexpression enhanced the anticancer functions of sevoflurane in CRC cells, while miR-637 inhibition showed opposite effects. WNT1 was confirmed to be a target of miR-637 and was inhibited by sevoflurane or miR-637. Importantly, knockdown of WNT1 reversed the carcinogenic effects mediated by miR-637 inhibitor in CRC cells treated with sevoflurane. Collectively, sevoflurane inhibited cell migration, invasion and induced apoptosis by regulating the miR-637/WNT1 axis in colorectal cancer, indicating a novel insight into the effective clinical implication for the anesthetic in CRC treatment.
结直肠癌（CRC）是一种常见的恶性肿瘤。有报道称，七氟醚参与了几种癌症的进展。然而，七氟醚在 CRC 进展中的分子机制尚不清楚。采用实时定量 PCR 和 Western blot 检测 miR-637 和 WNT1 的表达。通过 Transwell 测定、流式细胞术或 Western blot 分别检测细胞迁移、侵袭和凋亡。通过荧光素酶报告基因测定、RNA 免疫沉淀测定和下拉测定证实 WNT1 与 miR-637 之间的相互作用。我们发现七氟醚可抑制 CRC 细胞的迁移和侵袭，但诱导细胞凋亡。此外，CRC 组织和细胞中的 miR-637 水平降低，但可被七氟醚挽救。miR-637 过表达增强了七氟醚对 CRC 细胞的抗癌作用，而 miR-637 抑制则显示出相反的效果。WNT1 被证实是 miR-637 的靶基因，并被七氟醚或 miR-637 抑制。重要的是，WNT1 的敲低逆转了 miR-637 抑制剂处理的七氟醚处理的 CRC 细胞中的致癌作用。总之，七氟醚通过调节 miR-637/WNT1 轴抑制结直肠癌细胞的迁移、侵袭并诱导细胞凋亡，为麻醉在 CRC 治疗中的有效临床应用提供了新的见解。
