Sevoflurane induces apoptosis and inhibits the growth and motility of colon cancer in vitro and in vivo via inactivating Ras/Raf/MEK/ERK signaling

• Published in: Life sciences (1973) Vol. 239; p. 116916
• Main Authors: Yang, Xiao, Zheng, Yao-tun, Rong, Wei
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 15.12.2019; Elsevier BV
• Subjects: Animals; Apoptosis; Apoptosis - drug effects; Autophagy; Autophagy - drug effects; Cadherins - metabolism; Carbon dioxide; Cell cycle; Cell Cycle - drug effects; Cell Line, Tumor; Cell Movement - drug effects; Cell proliferation; Cell Proliferation - drug effects; China; Colon; Colon cancer; Colonic Neoplasms - metabolism; Colonic Neoplasms - physiopathology; Colorectal cancer; E-cadherin; Epithelial-Mesenchymal Transition - drug effects; ERK signaling pathway; Extracellular signal-regulated kinase; G1 phase; Growth; Humans; In vivo methods and tests; Male; MAP Kinase Signaling System - drug effects; Mesenchyme; Metabolic pathways; Mice; Mice, Inbred BALB C; Mice, Nude; Motility; N-Cadherin; Phagocytosis; Proteins; raf Kinases - drug effects; Raf protein; ras Proteins - drug effects; Sevoflurane; Sevoflurane - metabolism; Sevoflurane - pharmacology; Signal transduction; Signal Transduction - drug effects; Signaling; Tumors; Vimentin; China; Sevoflurane; Colon cancer; Motility; Growth; ERK signaling pathway
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2019.116916

To investigate the effects of sevoflurane on proliferation, cell cycle, apoptosis, autophagy, invasion and epithelial-mesenchymal transition of colon cancer cell line SW480, and to explore its possible mechanism. SW480 and SW620 cells were treated with a mixture of 95% O2+5% CO2 containing different concentrations of sevoflurane (1.7% SAV, 3.4% SAV and 5.1% SAV) for 6 h. Meanwhile, we performed a rescue experiment by treating cells with the ERK pathway activator LM22B-10 prior to treatment of cells with 5.1% sevoflurane。 High concentration (5.1%) of sevoflurane significantly inhibited the proliferation and invasion of cells, causing G0/G1 phase arrest and promoted apoptosis and autophagy. 5.1% sevoflurane can participate in the regulation of EMT by regulating the expression of E-cadherin, Vimentin and N-cadherin proteins. LM22B-10 promoted proliferation and invasion of cancer cells and inhibited apoptosis and autophagy, while 5.1% sevoflurane could reverse the effect of LM22B-10 on the biological characteristics of cells. Sevoflurane can significantly inhibit tumor growth in SW480 cells transplanted nude mice. Moreover, 5.1% sevoflurane significantly increased the expression of p-Raf, p-MEK1/2, and p-ERK1/2 in SW480 cells and tumor tissues without affecting p-JNK and p-p38 proteins, meanwhile, 5.1% sevoflurane can inhibit the activation of ERK signaling pathway by LM22B-10 in vitro and in vivo. Sevoflurane can inhibit the proliferation and invasion of colon cancer cells, induce apoptosis and autophagy, and participate in the regulation of epithelial-mesenchymal transition, which may be related to its inhibition of the ERK signaling pathway. [Display omitted]