Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, China.
National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
Cell Transplant. 2022 Jan-Dec;31:9636897221104447. doi: 10.1177/09636897221104447.
Recent evidence has indicated that inhalational anesthetics may affect the growth and malignant potential of tumor cells and ultimately influence tumor recurrence after surgery. Sevoflurane, a volatile anesthetic, is used extensively in hepatectomy. However, the effect of sevoflurane on the growth of hepatocellular carcinoma (HCC) cells remains unknown. The aim of this study was to explore the effects of sevoflurane on HCC metastasis and its potential mechanisms in the human HCC cell lines, HepG2 and SMMC7721. HepG2 and SMMC7721 cells were treated with 1.7%, 3.4%, and 5.1 % sevoflurane for 6 h. Cell migration was analyzed using invasion, migration, and scratch assays. Based on previous literature, several microRNAs (miRNAs) were screened to determine regulatory miRNA targets of sevoflurane in HepG2 and SMMC7721 cells; miR-665 was detected as a potential target and overexpressed or inhibited in HepG2 and SMMC7721 cells by a lentiviral system. The p-ERK/MMP pathway was also measured by western blotting. Sevoflurane inhibited the migration and invasion of HCC cells in a dose-dependent manner. It also inhibited miR-665 expression in HCC cells. We further observed that sevoflurane inhibited HCC metastasis via miR-665. Sevoflurane-induced downregulation of miRNA-665 led to phosphorylation of ERK and matrix metalloproteinase (MMP-9) via suppression of SPRED1. These results demonstrated that sevoflurane may inhibit invasion and migration via the p-ERK/MMP-9 signaling pathway in HCC cells.
最近的证据表明，吸入麻醉剂可能会影响肿瘤细胞的生长和恶性潜能，并最终影响手术后的肿瘤复发。七氟醚是一种挥发性麻醉剂，广泛应用于肝切除术。然而，七氟醚对肝细胞癌（HCC）细胞生长的影响尚不清楚。本研究旨在探讨七氟醚对人 HCC 细胞系 HepG2 和 SMMC7721 转移的影响及其潜在机制。用 1.7%、3.4%和 5.1%七氟醚处理 HepG2 和 SMMC7721 细胞 6 小时。通过侵袭、迁移和划痕实验分析细胞迁移。根据先前的文献，筛选了几种 microRNAs（miRNAs），以确定 HepG2 和 SMMC7721 细胞中七氟醚的调节 miRNA 靶标；miR-665 被检测为潜在的靶标，并通过慢病毒系统在 HepG2 和 SMMC7721 细胞中过表达或抑制。p-ERK/MMP 通路也通过 Western blot 进行测量。七氟醚以剂量依赖的方式抑制 HCC 细胞的迁移和侵袭。它还抑制 HCC 细胞中 miR-665 的表达。我们进一步观察到，七氟醚通过 miR-665 抑制 HCC 转移。七氟醚诱导的 miR-665 下调通过抑制 SPRED1 导致 ERK 和基质金属蛋白酶（MMP-9）的磷酸化。这些结果表明，七氟醚可能通过 HCC 细胞中的 p-ERK/MMP-9 信号通路抑制侵袭和迁移。
