舒芬太尼通过Notch信号通路对前列腺癌细胞的影响  

Effects of sufentanil of prostate cancer cells through Notch signaling pathway

作　　者：李进岚 方晓[3] 黄银芳 郦萍 LI Jin-lan;FANG Xiao;HUANG Yin-fang;LI Ping(Department of Anesthesiology,Keqiao District Hospital of Traditional Chinese Medicine,Shaoxing 312030,Zhejiang Province,China;Operation Room,General Hospital of Medical Community,Keqiao District Hospital of Traditional Chinese Medicine,Shaoxing 312030,Zhejiang Province,China;Department of Anesthesiology,Sir Run Run Shaw Hospital Zhejiang University School of Medicine,Hangzhou 310009,Zhejiang Province,China)

机构地区：[1]绍兴市柯桥区中医医院医共体总院麻醉科,浙江绍兴312030 [2]绍兴市柯桥区中医医院医共体总院手术室,浙江绍兴312030 [3]浙江大学医学院附属邵逸夫医院麻醉科,浙江杭州310009

出　　处：《中国临床药理学杂志》2022年第12期1344-1348,共5页The Chinese Journal of Clinical Pharmacology

摘　　要：目的研究舒芬太尼通过Notch信号通路影响前列腺癌细胞增殖、凋亡和细胞周期的功能机制。方法对人前列腺癌细胞LNCaP进行培养,将LNCaP细胞随机分为对照组(Control组)、舒芬太尼低剂量组、舒芬太尼中剂量组、舒芬太尼高剂量组、舒芬太尼组和舒芬太尼+Notch1组;舒芬太尼低、中、高剂量组分别用2,10,50 ng·mL^(-1)舒芬太尼处理,舒芬太尼组用50 ng·mL^(-1)舒芬太尼处理,舒芬太尼+Notch1组用50 ng·mL^(-1)舒芬太尼与Notch1共同处理。通过细胞计数法-8(CCK-8)检测各组细胞增殖情况;用流式细胞术检测各组细胞凋亡情况及周期进程;用蛋白质印迹(Western blot)法检测LNCaP细胞凋亡及Notch信号通路相关蛋白表达情况。结果CCK-8检测可知,与对照组相比,舒芬太尼低、中、高剂量组72 h的光密度(OD)值显著降低,且具有剂量依赖性(均P<0.05);与舒芬太尼组相比,随着作用时间的延长,舒芬太尼+Notch1组72 h的OD值逐渐增加(P<0.05)。对照组和舒芬太尼低、中、高剂量组的细胞凋亡率分别为(4.16±0.53)%,(8.97±0.81)%,(15.75±1.87)%和(20.27±2.06)%;Notch信号通路相关蛋白Notch1的表达水平分别为0.88±0.08,0.66±0.05,0.51±0.07和0.36±0.08;NICD的表达水平分别为0.96±0.08,0.70±0.05,0.60±0.07和0.46±0.08;Hes1的表达水平分别为0.98±0.06,0.72±0.08,0.60±0.05和0.44±0.04。舒芬太尼低、中、高剂量组与对照组比较,差异均有统计学意义(均P<0.05)。与对照组相比,随着舒芬太尼浓度的增加,舒芬太尼低、中、高剂量组凋亡相关蛋白Cl-caspase-3及Bax表达水平逐渐增加(P<0.05),Bcl-2表达水平逐渐降低(P<0.05);流式细胞术检测可知,与对照组相比,随着舒芬太尼浓度的增加,G0/G1期的阻滞率升高(P<0.05),S期的阻滞率下降(P<0.05),G2/M期的阻滞率未发生明显变化。结论舒芬太尼通过Notch信号通路,能够抑制前列腺癌细胞增殖促进其发生凋亡。Objective To investigate the functional mechanism of sufentanil affecting prostate cancer cell proliferation,apoptosis and cell cycle through Notch signaling pathway.Methods The human prostate cancer cells LNCaP were cultured and randomly divided into control group,sufentanil low dose group,sufentanil medium dose group,sufentanil high dose group,sufentanil group and sufentanil+Notch1 group.The sufentanil low,medium and high dose groups were treated with 2,10 and 50 ng·mL^(-1) sufentanil,respectively.Sufentanil group was treated with 50 ng·mL^(-1) sufentanil,sufentanil+Notch1 group was treated with 50 ng·mL^(-1) sufentanil together with Notch1.The cell proliferation of each group was detected by cell counting kit-8(CCK-8).The apoptotic status and cycle progression of cells in each group were detected by flow cytometry.Western blot was used to detect the apoptosis of LNCaP cells and the expression of Notch signaling pathway related proteins.Results CCK-8 test showed that,compared with control group,the 72 h OD values of sufentanil low,medium and high dose groups were gradually decreased with dose depended(all P<0.05).Compared with sufentanil group,the 72 h OD value of sufentanil+Notch1 group were gradually increased(P<0.05).The apoptosis rates in control group and sufentanil low,medium and high dose groups were(4.16±0.53)%,(8.97±0.81)%,(15.75±1.87)%and(20.27±2.06)%;the expression levels of Notch signaling pathway related protein Notch1 were 0.88±0.08,0.66±0.05,0.51±0.07 and 0.36±0.08;the expression levels of NICD were 0.96±0.08,0.70±0.05,0.60±0.07 and 0.46±0.08;the expression levels of Hes1 were 0.98±0.06,0.72±0.08,0.60±0.05 and 0.44±0.04,respectively.The difference were all statistical compared between control group and sufentanil low,medium and high dose groups(all P<0.05).Compared with control group,with the increase of sufentanil concentration,the expression levels of apoptosis-related proteins Cl-caspase-3 and Bax in sufentanil low,medium and high dose groups were increased gradually(P<0.05)

关 键 词：舒芬太尼 NOTCH信号通路 前列腺癌细胞 增殖 凋亡 细胞周期 

分 类 号：R971.2[医药卫生—药品]