Drug Design, Development and Therapy (Dec 2019)
Sevoflurane Inhibits Proliferation and Invasion of Human Ovarian Cancer Cells by Regulating JNK and p38 MAPK Signaling Pathway
Abstract
Kai Kang, Yue Wang Department of Anesthesiology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, People’s Republic of ChinaCorrespondence: Yue WangDepartment of Anesthesiology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, No. 251 Yaojiayuan Road, Beijing 100026, People’s Republic of ChinaTel +86-13671077406Email [email protected]: 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
