PDTC联合泰素帝对SGC-7901人胃癌细胞抑制效应及其机制

Inhibitory effects of PDTC combined with taxotere on SGC-7901 human gastric cancer cells and its mechanisms

目的研究PDTC合并泰素帝对SGC-7901人胃癌细胞的抑制效应及其机制。方法应用MTT法观察PDTC及泰素帝对SGC-7901细胞的增殖抑制效应,采用流式细胞术检测不同处理后SGC-7901细胞凋亡率的变化,采用实时荧光定量PCR法测定c-IAP2及XIAP基因表达的改变,采用Western印迹法检测NF-κB P65、I-κB蛋白表达的改变。结果 PDTC组、泰素帝组及联合用药组的细胞活力都明显比对照组降低(P<0.05),与相应的泰素帝组相比,联合用药组降低明显(P<0.01);PDTC、泰素帝及联合用药组的凋亡率高于对照组(P<0.01),联合用药组细胞凋亡率明显升高,达到29.37%,与泰素帝及PDTC单药组相比,差异有统计学意义(P<0.05);PDTC组XIAP及c-IAP2 mRNA表达较对照组下降,泰素帝组XIAP及c-IAP2 mRNA表达较对照组升高,联合用药组XIAP及c-IAP2 mRNA表达较对照组、泰素帝组明显下降(P<0.01);泰素帝处理后胞核NF-κB P65含量增加(P<0.01),而PDTC联合作用后胞浆及胞核NF-κB P65含量较泰素帝组及对照组明显降低(P<0.01)。结论泰素帝与PDTC均能抑制SGC-7901细胞增殖,诱导细胞凋亡,其机制可能与PDTC可拮抗泰素帝的NF-κB激活、抑制其下游凋亡抑制蛋白基因表达有关。

Objective To investigate the inhibitory effects of PDTC combined with taxotere on human gastric carcinoma cell line SGC-7901 and its mechanisms. Methods The cultured SGC-7901 cells w ere treated w ith PDTC,taxotere or PDTC plus taxotere. The anti-proliferation effects of PDTC and taxotere w ere determined by MTT assay; the apoptosis rate w as examined by flow cytometer; the expressions of c-IAP2 and XIAP mRNA w ere detected by Real-Time PCR; and the expressions of NF-κB P65 and IκB protein were measured by Western blotting method. Results The viabilities of SGC-7901 cells in PDTC group,taxotere group and the combination group w ere low er than that in control group（ P ＆lt; 0. 05）; compared w ith the corresponding taxotere group,the cell viabilities of combined treatment group w ere significantly low er（ P ＆lt; 0. 01）. Cell apoptosis rates in PDTC group,taxotere group and combination group w ere higher than that in control group（ P ＆lt; 0. 01）; the cell apoptosis rate of combined treatment group w as 29. 37%,w hich w as significantly higher than those in taxotere and PDTC monotherapy group（ P ＆lt; 0. 05）. The expressions of XIAP and c-IAP2 mRNA in PDTC group w ere decreased,w hile those w ere increased in the taxotere group,and the expressions of tw o genes in combination group w ere decreased significantly compared w ith the control and taxotere groups（ P ＆lt; 0. 01）. The nucleus NF-κB P65 content in taxotere group w as increased significantly（ P ＆lt; 0. 01）, w hile that in combination group w as decreased significantly compared w ith taxotere and the control groups（ P ＆lt; 0. 01）. Conclusion Both taxotere and PDTC can inhibit proliferation and induce apoptosis in SGC-7901 cells. PDTC may inhibit docetaxel-induced NF-κB activation and gene expression of its dow nstream apoptosis protein inhibitors.