摘要
目的 探究咪达唑仑(midazolam, MDZ)通过调控腺苷酸活化蛋白激酶(AMP-activated protein kinase,AMPK)/沉默信息调节因子相关酶1(silent information regulator 1,SIRT1)/过氧化物酶体增殖物激活受体γ辅激活因子1α(peroxisome proliferator-activated receptor γ coactivator 1α,PGC-1α)通路对子宫内膜癌(endometrial cancer,EC)细胞增殖、迁移及凋亡的影响。方法 将人EC细胞(Ishikawa)分为Control组(常规培养)、MDZ-L组(5μmol/L)、MDZ-M组(10μmol/L)、MDZ-H组(20μmol/L)、Compound C组(20μmol/L MDZ+10μmol/L AMPK抑制剂Compound C)。MTT和克隆形成实验检测细胞的增殖;Transwell实验检测细胞的迁移和侵袭;流式细胞仪检测细胞的凋亡率;Western blot检测细胞中MMP-2、Bcl-2、AMPK、SIRT1、PGC-1α蛋白的表达。结果 MDZ-L组、MDZ-M组、MDZ-H组细胞A_(490)值、克隆数、迁移数、侵袭数、MMP-2、Bcl-2蛋白表达低于Control组(P<0.05),细胞凋亡率、p-AMPK/AMPK、SIRT1、PGC-1α蛋白表达高于Control组(P<0.05);Compound C组细胞A_(490)值、克隆数、迁移数、侵袭数、MMP-2、Bcl-2蛋白表达高于MDZ-H组(P<0.05),细胞凋亡率、p-AMPK/AMPK、SIRT1、PGC-1α蛋白表达低于MDZ-H组(P<0.05)。结论 MDZ可抑制EC细胞的增殖、迁移及凋亡,可能是通过激活AMPK/SIRT1/PGC-1α通路实现的。
Objective This study aimed to investigate the effects of midazolam(MDZ)on proliferation,migration,and apoptosis in endometrial cancer(EC)cells and elucidate its potential mechanism through the AMP-activated protein kinase(AMPK)/silent information regulator 1(SIRT1)/peroxisome proliferator-activated receptorγcoactivator 1α(PGC-1α)pathway.Methods Human EC cells(Ishikawa)were assigned into Control group(conventional culture),MDZ-L group(5μmol/L),MDZ-M group(10μmol/L),MDZ-H group(20μmol/L),and Compound C group(20μmol/L MDZ+10μmol/L AMPK inhibitor Compound C).MTT and colony formation assays were performed to assess cell proliferation.Transwell assay was performed to detect cell migration and invasion.Flow cytometry was used to assess the apoptosis rate of cells.Western blot was used to assess MMP-2,Bcl-2,AMPK,SIRT1,and PGC-1αproteins in cells.Results The MDZ-L group,MDZ-M group,and MDZ-H group had lower cell A490 value,clone number,migration number,invasion number,MMP-2,and Bcl-2 proteins(P<0.05),and higher cell apoptosis rate,p-AMPK/AMPK,SIRT1,and PGC-1αproteins than the Control group(P<0.05).The Compound C group had higher cell A490 value,clone number,migration number,invasion number,MMP-2 and Bcl-2 proteins(P<0.05),and lower cell apoptosis rate,p-AMPK/AMPK,SIRT1,and PGC-1αproteins than MDZ-H group(P<0.05).Conclusion Midazolam suppresses proliferation and migration while inducing apoptosis in EC cells,likely through activation of the AMPK/SIRT1/PGC-1αpathway.
作者
姚文杰
李秋影
赵石磊
王慧娟
马江涛
王亚凡
常欢
YAO Wenjie;LI Qiuying;ZHAO Shilei;WANG Huijuan;MA Jiangtao;WANG Yafan;CHANG Huan(Anesthesiology Department of Shijiazhuang Maternal and Child Health Hospital,Shijiazhuang,Hebei 050000,China;Obstetrics and Gynecology Department of Shijiazhuang Maternal and Child Health Hospital,Shijiazhuang,Hebei 050000,China)
出处
《中国优生与遗传杂志》
2025年第8期1745-1750,共6页
Chinese Journal of Birth Health & Heredity
基金
河北省卫生健康委员资助项目(20240731)
