Sevoflurane suppresses cell viability and invasion and promotes cell apoptosis in colon cancer by modulating exosome‑mediated circ‑HMGCS1 via the miR‑34a‑5p/SGPP1 axis

Oncol Rep. 2020 Dec;44(6):2429-2442. doi: 10.3892/or.2020.7783. Epub 2020 Sep 29.

Abstract

As a novel halogenated hydroxyl ether‑inhaled general anesthetic, sevoflurane has been reported to affect the progression of diverse human cancers. In the present study, we aimed to explore the functions and underlying mechanisms of sevoflurane in colon cancer. MTT assay, flow cytometric analysis and Transwell assay were conducted to evaluate cell viability, apoptosis and invasion, respectively. Western blot analysis was performed to determine the protein level of sphingosine‑1‑phosphate phosphatase 1 (SGPP1). The morphology and size of exosomes were analyzed by TEM and NTA. The levels of circular RNA 3‑hydroxy‑3‑methylglutaryl‑CoA synthase 1 (circ‑HMGCS1), microRNA (miR)‑34a‑5p and SGPP1 mRNA were examined by RT‑qPCR. Dual‑luciferase reporter and RNA RIP assays were utilized to explore the interaction between miR‑34a‑5p and circ‑HMGCS1 or SGPP1. A murine xenograft model was established to investigate the effect of circ‑HMGCS1 in vivo. As a result, it was determined that sevoflurane suppressed cell viability and invasion and induced apoptosis in colon cancer in a dose‑dependent way. Exosomal circ‑HMGCS1 was increased in the serums and cells of colon cancer patients. Circ‑HMGCS1 was downregulated by sevoflurane treatment in colon cancer cells and circ‑HMGCS1 overexpression could restore the effect of sevoflurane on colon cancer cell development. miR‑34a‑5p was a target of circ‑HMGCS1 and miR‑34a‑5p inhibition reversed the effect of circ‑HMGCS1 silencing on colon cancer cell progression. Moreover, circ‑HMGCS1 knockdown suppressed SGPP1 expression via sponging miR‑34a‑5p. Knockdown of circ‑HMGCS1 blocked tumor growth in vivo. In conclusion, sevoflurane inhibited colon cancer progression by modulating the exosome‑transmitted circ‑HMGCS1/miR‑34a‑5p/SGPP1 axis.