Kang Kai, Wang Yue
Department of Anesthesiology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, People's Republic of China.
Drug Des Devel Ther. 2019 Dec 31;13:4451-4460. doi: 10.2147/DDDT.S223581. eCollection 2019.
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.
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.
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.
Sevoflurane affected cell biological activities in OC by regulating JNK and p38 MAPK signaling pathway.
七氟醚是一种卤族吸入性麻醉剂，我们旨在探究七氟醚对人卵巢癌（OC）增殖和侵袭的影响及其机制。
将OC细胞系分为4组，包括对照组、七氟醚低浓度（1.7%）组、中浓度（3.4%）组和高浓度（5.1%）组。分别采用流式细胞术和MTT法检测细胞凋亡和增殖情况。运用Transwell法检测细胞迁移和侵袭能力。采用qRT-PCR和蛋白质免疫印迹法评估基因和蛋白表达。通过蛋白质免疫印迹法评估丝裂原活化蛋白激酶（MAPK）信号通路相关蛋白的表达。向高浓度组分别加入p38和JNK抑制剂，以分析七氟醚与OC中调节MAPK通路之间的关系。构建裸鼠模型以探究七氟醚对OC肿瘤体内生长的影响。
七氟醚在体外和体内均抑制OC增殖。它还能以剂量依赖的方式促进OC细胞凋亡。七氟醚抑制OC细胞迁移和侵袭，且这些作用与七氟醚剂量呈正相关。此外，七氟醚处理抑制了增殖细胞核抗原（PCNA）、Twist、裂解的半胱天冬酶-3/半胱天冬酶-3、基质金属蛋白酶-2（MMP-2）和基质金属蛋白酶-9（MMP-9）的表达。另外，七氟醚抑制JNK和p38 MAPK的磷酸化。当MAPK通路被阻断时，七氟醚处理后细胞增殖、凋亡、迁移和侵袭活性恢复。
七氟醚通过调节JNK和p38 MAPK信号通路影响OC中的细胞生物学活性。
