七氟醚调控卵巢癌细胞的增殖、迁移、侵袭和凋亡的机制

Effects and molecular mechanism of sevoflurane on the proliferation,migration,invasion and apoptosis of ovarian cancer cells

目的探讨七氟醚对卵巢癌细胞的增殖、迁移侵袭和凋亡的影响及分子机制。方法选取2017年1月至2019年1月30例卵巢癌患者癌组织和癌旁组织;将卵巢癌细胞株SKOV3分为不同浓度七氟醚组、对照组、miR-NC组、miR-143-3p组、2%七氟醚+anti-miR-NC组、2%七氟醚+anti-miR-143-3p组。实时荧光定量PCR(RT-qPCR)检测miR-143-3p表达;四甲基偶氮唑盐比色法(MTT)检测细胞活性;Transwell检测细胞迁移和侵袭;流式细胞术检测细胞凋亡;蛋白质印迹(Western blot)法检测蛋白表达。结果与癌旁组织比较,卵巢癌组织中miR-143-3p表达水平降低(P<0.05)。不同浓度七氟醚处理后的SKOV3细胞中,细胞活性降低,细胞迁移、侵袭数降低,细胞凋亡率升高,CyclinD1、MMP-2、MMP-9、Bcl-2表达水平降低,p21、Bax表达水平升高,miR-143-3p表达水平升高,且呈剂量依赖性(P<0.05)。上调miR-143-3p,SKOV3细胞活性降低,细胞迁移、侵袭数降低,细胞凋亡率升高,CyclinD1、MMP-2、MMP-9、Bcl-2表达水平降低,p21、Bax表达水平升高(P<0.05)。下调miR-143-3p逆转了七氟醚对卵巢癌SKOV3细胞增殖、迁移侵袭和凋亡的影响。结论七氟醚可能通过上调miR-143-3p的表达抑制卵巢癌细胞增殖、迁移侵袭,并促进细胞凋亡。

Objective To investigate the effects and molecular mechanism of sevoflurane on the proliferation,migration,invasion and apoptosis of ovarian cancer cells.Methods Thirty cases of ovarian cancer tissues and adjacent tissues of patients with ovarian cancer who were treated in our hospital from January 2017 to January 2019 were selected,and ovarian cancer cells SKOV3 were divided into different concentrations of sevoflurane groups,control group,miR-NC group,miR-143-3p group,2%sevoflurane+anti-miR-NC group,2%sevoflurane+anti-miR-143-3p group.Real-time fluorescence quantitative PCR(RT-qPCR)was used to detect miR-143-3p expression;tetramethylazozolate colorimetric method(MTT)was used to detect cell activity;Transwell was used to detect cell migration and invasion;flow cytometry was used to detect apoptosis;the protein expression was detected by Western Blot.Results Compared with those in adjacent tissues,the expression levels of miR-143-3p in ovarian cancer tissues were significantly decreased(P<0.05).In the SKOV3 cells treated by different concentrations of sevoflurane,cell viability,cell migration and invasion number were significantly decreased,however,the cell apoptosis rate was increased,moreover,the expression levels of CyclinD1,MMP-2,MMP-9,Bcl-2 were significantly decreased,but,the expression levels of p21,Bax and miR-143-3p were significantly increased,with a dose-dependent manner(P<0.05).In addition the up-regulation of miR-143-3p reduced the activity of SKOV3 cells,decreased the number of cell migration and invasion,increased the apoptosis rate,decreased the expressions of CyclinD1,MMP-2,MMP-9,Bcl-2,and significantly increased the expression levels of p21 and Bax(P<0.05).Moreover down-regulation of miR-143-3p reversed the effects of sevoflurane on the proliferation,migration,invasion and apoptosis of ovarian cancer SKOV3 cells.Conclusion Sevoflurane may inhibit the proliferation,migration and invasion of ovarian cancer cells and promote apoptosis by up-regulating the expression of miR-143-3p.