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

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, cleavedcaspase-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.

Anesthetics or anesthetic techniques and cancer surgical outcomes: a possible link

“…These factors in combination have alluded to sevoflurane’s involvement in inhibiting the progression of ovarian cancer (concentrations of sevoflurane ranging from 0.5% to 10%, depending on cell type) [ 48 ]. The effects of sevoflurane were corroborated in a study by Kang and Wang [ 49 ], which had also shown an inhibition of ovarian cancer proliferation (sevoflurane low concentration (1.7%), medium concentration (3.4%) and high concentration (5.1%) groups); however, this was through the repression of the phosphorylation of JNK and p38 MAPK signaling pathways. In contrast, a study that utilized higher concentrations of volatile anesthetics (sevoflurane 3.6%, isoflurane 2%, and desflurane 10.3%), but with a shorter incubation period, had revealed a significant increase in VEGF-A, MMP-11, CXCR2, and TGF-β genes, which collectively may enhance ovarian cancer proliferation [ 50 ].…”

<p>Anti-Tumor Xanthones from <em>Garcinia nujiangensis</em> Suppress Proliferation, and Induce Apoptosis via PARP, PI3K/AKT/mTOR, and MAPK/ERK Signaling Pathways in Human Ovarian Cancers Cells</p>

“…In this study, bioassay-directed fractionation of the fruit of G. nujiangensis, led to a new xanthone named nujiangexanthone G (1) together with two known analogues: isojacareubin (2), and 1,5,6-trihydroxy-2-prenyl-6′,6′dimethyl-2H-pyrano(2′,3′: 3,4) xanthone (3). The activity test suggested that 2 had moderate cytotoxic activity against human OC cell lines HEY and ES-2 with the IC 50 values of 6.5 ± 0.4 μM, 9.5 ± 0.3 μM, respectively, respectively.…”

“…Therefore, novel therapeutic strategies are urgently required which can improve survival in OC patients. 3 Poly (ADP-ribose) polymerase (PARP), a family of proteins involved in DNA damage repair, genomic stability, and programmed cell death. The development of PARP inhibitors (PARPi) has succeed in the treatment of OC.…”

Sevoflurane represses the migration and invasion of gastric cancer cells by regulating forkhead box protein 3

“…GC cells were exposed to sevoflurane (Merck KGaA, Darmstadt, Germany) at low (1.7% v/v), medium (3.4% v/v), or high concentrations (5.1% v/v), as described previously. 21,22…”