SKI-Ⅱ促胃癌SGC7901细胞凋亡的实验研究  

SKI-Ⅱ promoting apoptosis of SGC7901 cells

作　　者：朱祖安[1] 费素娟[1] 刘磊[2] 孙旻[1] 张秋月[1] 刘莹[2] 

机构地区：[1]徐州医学院附属医院消化内科,江苏徐州221000 [2]徐州医学院病理学教研室,江苏徐州221000

出　　处：《南京医科大学学报（自然科学版）》2011年第4期463-468,共6页Journal of Nanjing Medical University(Natural Sciences)

基　　金：江苏省教育厅自然科学基金(05KJD320234);江苏省卫生厅科研课题基金(Z201016)

摘　　要：目的:研究鞘氨醇激酶(sphingosine kinase,SphK)抑制剂SKI-Ⅱ对人胃癌SGC7901细胞凋亡的影响,并探讨其具体作用机制。方法:常规培养人胃癌SGC7901细胞,SKI-Ⅱ单用或联合顺铂(DDP)干预,流式细胞术检测细胞凋亡率;电镜下观察用药后细胞超微结构的改变;免疫细胞化学、Western blot检测药物作用后细胞中Sphk1、NF-κB、Bcl-2、Bax的表达。Pearson相关分析检测Sphk1与NF-κB、NF-κB与Bcl-2表达的相关性。结果:SKI-Ⅱ单用或联合DDP干预48 h后,SKI-Ⅱ5μmol/L组、SKI-Ⅱ10μmol/L组、DDP 2.5 mg/L组、DDP 2.5 mg/L+SKI-Ⅱ5μmol/L组和DDP 2.5 mg/L+SKI-Ⅱ10μmol/L组细胞凋亡率分别为(40.39±1.06)%、(45.58±0.75)%、(47.27±1.13)%、(53.64±1.11)%和(66.98±2.32)%。与阴性对照组比,差异均有统计学意义(P<0.05);电镜下观察到SGC7901细胞胞浆内出现凋亡小体;SGC7901细胞中Bax阳性表达率增加,Sphk1、NF-κB、Bcl-2阳性表达率减少。Sphk1与NF-κB、NF-κB和Bcl-2的表达呈正相关。结论:SKI-Ⅱ可以通过抑制细胞中Sphk1的表达从而下调NF-κB的表达,并升高Bax/Bcl-2的比例诱导人胃癌SGC7901细胞的凋亡。Objective：To study the effect and mechanism of sphingosine kinase inhibitor SKI-Ⅱ on the apoptosis of human gastric cancer cell SGC7901.Methods：SGC7901 cells were cultured and treated with SKI-Ⅱ alone or in combination with cisplatin（DDP）.The apoptosis of the tumor cells was analyzed by flow cytometry;the morphological changes were observed by electron microscopy;the expression of Sphk1,NF-κB,Bcl-2 and Bax were detected by immunocytochemistry and Western blot.Pearson analysis was used to detect the correlations between Sphk1 and NF-κB,NF-κB and Bcl-2.Results：After treated for 48 h,the apoptosis rates in SGC7901 treated with SKI-Ⅱ 5,10 μmol/L,DDP 2.5 mg/L,DDP 2.5 mg/L＋SKI-Ⅱ 5 μmol/L and DDP 2.5 mg/L＋SKI-Ⅱ 10 μmol/L were（40.39±1.06）%,（45.58±0.75）%,（47.27±1.13）%,（53.64±1.11）% and（66.98±2.32）%,respectively,compared with the control group[（18.46±1.64）%],the differences were significant（P 0.05）.Apoptotic bodies were found in SGC7901 cells by electron microscopy.The expression of Bax was increased,but the expression of Sphk1,NF-κB and Bcl-2 was decreased.And the correlations between Sphk1 and NF-κB,NF-κB and Bcl-2 were positive.Conclusion：SKI-Ⅱ could induce the apoptosis of SGC7901 cells through down-regulating the expression of Sphk1 and NF-κB,and increasing the ratio of Bax/Bcl-2.

关 键 词：SKI-Ⅱ SGC7901细胞 凋亡 

分 类 号：R735.2[医药卫生—肿瘤]