摘要
目的 探讨舒芬太尼(SUF)对卵巢癌细胞增殖、迁移和侵袭的影响,分析其机制是否与Notch-1/Hes信号通路有关.方法 将SKOV3细胞分为对照组(未处理)、低剂量SUF组(L-SUF组,0.01μmol/L)、中剂量SUF组(M-SUF组,0.1 μmol/L)、高剂量 SUF 组(H-SUF 组,1 μmol/L),DAPT 组(5 μmol/L Notch-1/Hes 信号通路阻断剂 DAPT)、H-SUF+Jagged1组(1 μmol/L SUF和400 μg/L Notch-1/Hes信号通路激动剂Jagged1).CCK-8试剂盒检测细胞活性;流式细胞仪检测细胞凋亡;划痕实验检测细胞迁移;Transwell法检测细胞侵袭;Western blot检测Notch 1、Notch 2、Notch 3、E-cadherin、N-cadherin、Snail、Hes-1、Hes-5蛋白表达.结果 与对照组比较,L-SUF、M-SUF组、H-SUF组、DAPT组OD值、侵袭细胞数、划痕愈合率、Snail、N-cadherin、Hes、Notch-1水平下降(P＜0.05);凋亡率、E-cadherin水平增加;与H-SUF组比较,H-SUF+Jagged1组OD值、侵袭细胞数、划痕愈合率、Snail、N-cadherin、Hes、Notch-1水平增加(P＜0.05);凋亡率、E-cadherin水平下降.结论 SUF可能通过抑制Notch-1/Hes信号通路,进而抑制卵巢癌细胞增殖、迁移和侵袭,促进卵巢癌细胞凋亡.
Abstract
Objective To investigate the effects of sufentanil(SUF)on ovarian cancer cell proliferation,migration and invasion,and to analyze whether the mechanism is related to the Notch-1/Hes signaling pathway.Methods SKOV3 cells were divided into control group(untreated),low-dose SUF group(L-SUF group,0.01 μmol/L),medium-dose SUF group(M-SUF group,0.1 μmol/L),high-dose SUF group(H-SUF group,1 μmol/L),DAPT group(5 μmol/L Notch-l/Hes signaling pathway blocker DAPT),and H-SUF+Jagged1 group(1 μmol/L SUF and 400 μg/L Notch-1/Hes signaling pathway agonist Jagged1).CCK-8 kit to detect SKOV3 cell activity,flow cytometry to detect SKOV3 cell apoptosis,scratch assay to detect SKOV3 cell migration ability,Transwell assay to detect SKOV3 cell invasion ability,Western blot to detect the expression of Notch 1,Notch 2,Notch 3,E-cadherin,N-cadherin,Snail,Hes-1,Hes-5 proteins.Results Compared with the control group,OD value,number of invading cells,scratch healing rate,Snail,N-cadherin,Hes,and Notch-1 levels were lower in the L-SUF,M-SUF,H-SUF,and DAPT groups(P＜0.05).Apoptosis rate,and E-cadherin levels were higher in the L-SUF,M-SUF,H-SUF,and DAPT groups(P＜0.05).And compared with the H-SUF group,OD value,number of invading cells,scratch healing rate,Snail,N-cadherin,Hes,and Notch-1 levels were higher in H-SUF+Jagged1 group(P＜0.05).Apoptosis rate,E-cadherin levels were lower(P＜0.05).Conclusion SUF may promote ovarian cancer cell apoptosis by inhibiting the Notch-1/Hes signaling pathway,which in turn inhibits ovarian cancer cell proliferation,migration and invasion.
基金项目
河北省中医药管理局中医药类科研计划项目(2019445)
石家庄市科技计划项目(221200343)
NETL
NSTL
万方数据