Sevoflurane Inhibits Proliferation and Invasion of Human Ovarian Cancer Cells by Regulating JNK and p38 MAPK Signaling Pathway

Abstract

Aim

Sevoflurane is a halogen inhaled anesthetic, and we aimed to probe the effect of sevoflurane on proliferation and invasion of human ovarian cancer (OC) and its mechanism.

Methods

OC cell lines were divided into 4 groups including control, sevoflurane low concentration (1.7%), medium concentration (3.4%) and high concentration (5.1%) groups. Flow cytometry and MTT assay were, respectively, employed to detect the cell apoptosis and proliferation. Transwell assay was applied to measure the cell migration and invasion viability. The gene and protein expressions were assessed using qRT-PCR and Western blot. The expressions of MAPK signaling pathway-related proteins were evaluated by Western blot. The p38 and JNK inhibitors were, respectively, added into the high concentration group to analyze the relationship between sevoflurane and modulatingmitogen-activated protein kinase (MAPK) pathway in OC. Nude mice models were constructed to explore the effect of sevoflurane on OC tumor growth in vivo.

Results

Sevoflurane inhibited OC proliferation in vitro and in vivo. It could also promote OC cell apoptosis in a dose-dependent manner. Sevoflurane suppressed the OC cell migration and invasion, and these effects were positively correlated with the dose of sevoflurane. Moreover, sevoflurane treatment inhibited the expressions of PCNA, Twist, cleaved-caspase-3/caspase-3, MMP-2 and MMP-9. In addition, sevoflurane repressed the phosphorylation of JNK and p38 MAPK. When the MAPK pathway was interdicted, the cell proliferation, apoptosis, migration and invasion activity were recovered after sevoflurane treatment.

Conclusion

Sevoflurane affected cell biological activities in OC by regulating JNK and p38 MAPK signaling pathway.

Keywords:

• ovarian cancer
• sevoflurane
• proliferation
• migration and invasion
• MAPK signaling pathway

Availability of data and materials

All data generated and/or analyzed during this study are included in this published article.

Author Contributions

Both authors contributed to data analysis, drafting and revising the article, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Disclosure

The authors declare that they have no competing interests.