Sevoflurane Inhibits Metastasis in Hepatocellular Carcinoma by Inhibiting MiR-665-Induced Activation of the ERK/MMP Pathway

Author:

Zhu Xiaoyan12,Peng Chuchu1,Peng Zhiyong3,Chang Ruimin24ORCID,Guo Qulian12

Affiliation:

1. Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, China

2. National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China

3. Department of Anesthesiology, Shenzhen Hospital, Southern Medical University, Guangdong, China

4. Department of Thoracic Surgery, Xiangya Hospital, Central South University, Changsha, China

Abstract

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.

Funder

Natural Science Foundation General Program of Hunan Province

Changsha Municipal Natural Science Foundation

Outstanding Youth Fund of Natural Science Foundation of Hunan Province

Innovation-Driven Project of Central South University

Hunan Science and Technology Innovation Talent Program-Excellent Postdoctoral Innovation Talent Project

Project of scientific research plan of Hunan provincial health commission

Natural Science Foundation of Hunan Province

China Postdoctoral Science Foundation Funded Project

Publisher

SAGE Publications

Subject

Transplantation,Cell Biology,Biomedical Engineering

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