右美托咪定对宫颈癌细胞HSP90/ERK通路及顺铂敏感性的影响

Effects of dexmedetomidine on HSP90/ERK pathway and cisplatin sensitivity in cervical cancer cells

目的探讨右美托咪定对宫颈癌细胞热休克蛋白90(HSP90)/细胞外信号调节激酶(ERK通路及顺铂敏感性的影响。方法体外培养人宫颈癌HeLa细胞,分为对照组、顺铂组、低浓度组和高浓度组。蛋白印迹(Western blot)法检测各组HeLa细胞中HSP90、ERK、p-ERK、DNA甲基转移酶1(DNMT1)、DNA聚合酶δ催化亚基(POLD1)、增殖细胞核抗原(PCNA)、Bcl-2相关X蛋白(Bax)蛋白表达情况;CCK-8法检测各组HeLa细胞增殖情况;流式细胞仪检测各组HeLa细胞凋亡情况。结果与对照组相比,顺铂组HeLa细胞中HSP90、p-ERK/ERK、DNMT1、POLD1、PCNA蛋白水平、OD值降低(P<0.05),而凋亡率、Bax蛋白水平升高(P<0.05);随着右美托咪定的添加及浓度的升高,HeLa细胞中HSP90、p-ERK/ERK、DNMT1、POLD1、PCNA蛋白水平、OD值依次降低(P<0.05),而凋亡率、Bax蛋白水平依次升高(P<0.05)。结论右美托咪定可抑制宫颈癌HeLa细胞中HSP90/ERK通路,增强HeLa细胞对顺铂的敏感性。

Objective To investigate the effects of dexmedetomidine on heat shock protein 90(HSP90)/extracellular signal regulated kinase(ERK)pathway and cisplatin sensitivity in cervical cancer cells.Methods Human cervical cancer HeLa cells were cultured in vitro and divided into control group,cisplatin group,low concentration group and high concentration group.Western blot was used to detect the expressions of HSP90,ERK,p-ERK,DNA methyltransferases1(DNMT1),DNA polymerase delta catalytic subunit gene 1(POLD1),proliferating cell nuclear antigen(PCNA),and Bcl-2 associated X protein(Bax)protein in HeLa cells;the proliferation of HeLa cells was detected by CCK-8 method;and the apoptosis of HeLa cells was detected by flow cytometry.Results Compared with those in the control group,the protein expression levels of HSP90,p-ERK/ERK,DNMT1,POLD1,PCNA and OD value of HeLa cells in cisplatin group were significantly lower(P<0.05),while the apoptosis rate and Bax protein expression level were significantly higher(P<0.05);with the addition and increase of dexmedetomidine,the protein expression levels of HSP90,p-ERK/ERK,DNMT1,POLD1,PCNA and OD value of HeLa cells decreased in turn(P<0.05)while the apoptosis rate and Bax protein expression level increased in turn(P<0.05).Conclusion Dexmedetomidine can inhibit the HSP90/ERK pathway in cervical cancer HeLa cells and enhance the sensitivity of HeLa cells to cisplatin.