Sphk1抑制剂PF543对非小细胞肺癌细胞凋亡及增殖的影响  

Effect of Sphk1-Specific Inhibitor PF543 on Apoptosis and Proliferation in Non-small Cell Lung Cancer Cells

作　　者：吴佳玉 智炎伟 高梦月 WU Jiayu;ZHI Yanwei;GAO Mengyue(Pharmacy Department,Luoyang Central Hospital Affiliated to Zhengzhou University,Luoyang 471000,China)

机构地区：[1]郑州大学附属洛阳中心医院药学部,河南洛阳471000

出　　处：《河南医学研究》2024年第19期3486-3489,共4页Henan Medical Research

摘　　要：目的探讨鞘氨醇激酶1(Sphk1)抑制剂PF543对非小细胞肺癌A549细胞的凋亡和增殖的影响。方法体外培养并采集非小细胞肺癌细胞株A549,采用不同浓度的PF543处理并将其记为A组(0μmol·L^(-1))、B组(10μmol·L^(-1))、C组(20μmol·L^(-1)),另选取健康人体肺细胞作为对照组。使用逆转录聚合酶链反应(RT-PCR)检测各组的Sphk1表达水平。使用CCK8试剂盒检测在不同浓度PF543作用下,A549细胞的增殖能力;使用流式细胞仪检测在不同浓度PF543作用下,A549细胞的凋亡率;使用Western blot检测在不同浓度PF543作用下,A549细胞的Caspase-3、Ki67、Sphk1的相对表达水平。结果A组的Sphk1 mRNA表达水平高于对照组(P<0.05);B组和C组的Sphk1 mRNA表达水平均低于A组,且C组低于B组(P<0.05)。在同一培养时间下,与A组相比,B组和C组的肿瘤细胞生长抑制率均升高,且C组高于B组(P<0.05);在同一浓度下,培养时间越长,肿瘤细胞生长抑制率越高(P<0.05)。与A组相比,B组和C组的A549细胞凋亡率均升高,且C组低于B组(P<0.05)。与A组相比,B组和C组Caspase-3的相对表达水平均升高,且C组高于B组(P<0.05);B组和C组Ki67、Sphk1的相对表达水平均降低,且C组低于B组(P<0.05)。结论Sphk1在非小细胞肺癌中高表达,PF543可下调A549细胞中Sphk1的表达水平,并且可抑制A549细胞增殖以及促进A549细胞凋亡,其作用机制可能在于PF543可上调Caspase-3表达水平以促进细胞凋亡、下调Ki67表达水平以抑制细胞增殖。Objective To investigate the effect of sphingosine kinase 1(Sphk1)inhibitor PF543 on apoptosis and proliferation of non-small cell lung cancer A549 cells.Methods Non-small cell lung cancer cell line A549 was cultured in vitro and collected.Different concentrations of PF543 were added to the collected A549 cells and recorded as group A(0μmol·L^(-1)),group B(10μmol·L^(-1)),group C(20μmol·L^(-1)),and then healthy human lung cells were selected as the control group.Reverse transcription polymerase chain reaction(RT-PCR)was used to detect the expression level of Sphk1 in each group.The proliferation ability of A549 cells under different concentrations of PF543 was detected by CCK8 kit.The apoptosis rate of A549 cells was detected by flow cytometry under different concentrations of PF543.Western blot was used to detect the relative expression levels of Caspase-3,Ki67,and Sphk1 in A549 cells under different concentrations of PF543.Results The expression level of Sphk1 mRNA in group A was higher than that in the control group(P<0.05).The expression levels of Sphk1 mRNA in group B and group C were lower than those in group A,and group C was lower than group B(P<0.05).At the same culture time,compared with group A,the tumor cell growth inhibition rates in both group B and group C increased,and group C was higher than group B(P<0.05).At the same concentration,the longer the culture time,the higher the inhibition rate of tumor cell growth(P<0.05).Compared with group A,the apoptosis rate of A549 cells in both group B and group C increased,and group C was lower than group B(P<0.05).Compared with group A,the relative expression level of Caspase-3 in group B and group C increased,and group C was higher than group B(P<0.05).The relative expression levels of Ki67 and Sphk1 in group B and group C decreased,and group C was lower than group B(P<0.05).Conclusion Sphk1 is highly expressed in non-small cell lung cancer.PF543 can downregulate the expression level of Sphk1 in A549 cells,inhibit A549 cell proliferation,and promote A5

关 键 词：鞘氨醇激酶1 PF543 非小细胞肺癌 凋亡 增殖 

分 类 号：R734.2[医药卫生—肿瘤]