Sevoflurane induction alleviates the progression of gastric cancer by upregulating the miR-34a/TGIF2 axis

H. Chen, X.-M. Zhu, Z.-L. Luo, Y.-J. Hu, X.-C. Cai, Q.-H. Gu

Department of Gastrointestinal Surgery, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China. guqh9199@163.com

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• Pharmacology

OBJECTIVE: This study aims to elucidate how sevoflurane affects the malignant progression of gastric cancer (GC) and its pharmacological mechanism.

MATERIALS AND METHODS: Dose-dependent and time-dependent regulations of sevoflurane on proliferation inhibition rate in AGS and BGC-823 cells were examined, and thus the optimal dose and treatment time of sevoflurane on GC cells were selected. Subsequently, proliferative and migratory abilities in sevoflurane-induced AGS and BGC-823 cells (3.4% sevoflurane induction for 6 h) were detected by CCK-8 and transwell assay, respectively. After sevoflurane induction, relative levels of miR-34a and TGIF2 in GC cells were determined by qRT-PCR and Western blot. Regulatory effects of miR-34a on GC cell phenotypes were also assessed. Furthermore, the in vivo function of miR-34a in GC growth was explored by generating xenografted GC in nude mice.

RESULTS: Sevoflurane induction time-dependently and dose-dependently enhanced proliferation inhibition rate in AGS and BGC-823 cells. The proliferative and migratory abilities in GC cells induced with 3.4% sevoflurane for 6 h were markedly attenuated. sevoflurane induction upregulated miR-34a, but downregulated TGIF2 in GC cells. TGIF2 was negatively regulated by miR-34a. Notably, overexpression of miR-34a inhibited proliferative and migratory abilities in sevoflurane-induced GC cells, and knockdown of miR-34a yielded the opposite results. In nude mice with xenografted GC tissues, sevoflurane treatment markedly reduced tumorigenic ability, which was improved by knockdown of miR-34a.

CONCLUSIONS: Sevoflurane weakens proliferative and migratory abilities in GC by upregulating miR-34a and downregulating TGIF2.

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