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作 者:夏秀丽[1] 张志广[2] 李熳[2] 闻淑军[2]
机构地区:[1]天津医科大学研究生院,300070 [2]天津医科大学第二医院
出 处:《天津医药》2011年第10期907-910,共4页Tianjin Medical Journal
摘 要:目的:研究塞来昔布及吡咯烷二硫氨基甲酸(PDTC)对人胃癌细胞株SGC-7901的生长抑制作用及其相关机制。方法:分别应用塞来昔布50、100μmol/L,PDTC50、100μmol/L及2药联合25/25、50/50μmol/L处理SGC-7901胃癌细胞,四甲基偶氮唑蓝(MTT)法检测细胞生长抑制率。TUNEL法检测细胞的原位凋亡。RT-PCR检测环氧合酶-2(COX-2)、核因子(NF)-κB、caspase-3mRNA的表达。结果:塞来昔布、PDTC及2药联合作用于胃癌细胞72h细胞的生长均受到抑制(P<0.05),72h时25/25μmol/L的2药联合组与50μmol/L塞来昔布组相比,细胞的生长抑制率无明显差异(P>0.05),50/50μmol/L的2药联合组细胞生长抑制率高于100μmol/L的单独用药组(P<0.01)。100μmol/L的单独用药组和50/50μmol/L的2药联合组在作用于细胞24h后,细胞凋亡指数均高于阴性对照组,且2药联合组凋亡指数高于单独用药组(P<0.01)。100μmol/L的塞来昔布及PDTC单独作用于细胞12h后均可见COX-2、NF-κB表达降低(P<0.05),100μmol/L的塞来昔布和PDTC及2种浓度的2药联合caspase-3表达升高(P<0.05)。结论:塞来昔布与PDTC联合应用具有显著抗胃癌细胞增殖,促进其凋亡的作用,其机制可能与抑制COX-2、NF-κB的表达,促进caspase-3表达有关。Objective: To investigate the inhibitory effect of celecoxib combined with pyrrolidine dithiocarbamate (PDTC) on human gastric cancer cell line SGC-7901, and its mechanism thereof. Methods: SGC-7901 cells were treated in vitro with celecoxib (50 and 100 μmol/L), PDTC (50 and 100 μmol/L) and 2-drug combination (25/25 and 50/50 μmol/L) re- spectively. The methyl thiazolyl tetrazolium (MTT) assay was used to measure the growth inhibition rate of ceils. TUNEL assay was used to measure the in situ apoptosis of gastric cancer cells. The expression levels of cyclooxygenase-2 (COX-2), nuclear factor (NF)-KB and caspase-3 mRNA were detected by RT-PCR. Results: The growth of gastric cancer cells were inhibited after 72 h treatment with celeeoxib, PDTC or 2-drug combination (P 〈 0.05), but there was no significant difference in the growth inhibition rate between combination group (25/25 μmol/L) and celecoxib group (50 μmol/L, P 〉 0.05). There was a higher inhibitory effect in combination group (50/50 μmol/L) than that of single drug group (100 μmol/L, P 〈 0.01). After 24-h treatment by celecoxib (100 μmol/L), PDTC (100 μmol/L) or 2-drug combination (50/50 μmol/L), the apoptosis index was significantly higher than that of negative control, and there was a higher apoptosis index in 2-drug combination group than that of single drug group (P 〈 0.01). The expression levels of COX-2 and NF-kB were decreased (P 〈 0.05), when cells were exposed to celecoxib (100 μmol/L) or PDTC (100 μmol/L) for 12 hours. The expresion level of caspass-3 was increased when cells were exposed to celecoxib(100 μmol/L), PDTC(100 μmol/L) and 2-drug combination(P 〈 0.05). Conclusion: Combination of eelecoxib and PDTC can inhibit the proliferation and promote the apoptosis of gastric cancer cells, which may be associated with inhibition of NF-κB and COX-2 expression, and the promotion of the expression of caspase-3.
关 键 词:胃肿瘤NF-κB细胞凋亡环氧化酶2消炎药 非甾体类塞来昔布吡咯烷类SGC-7901
分 类 号:R151.2[医药卫生—营养与食品卫生学]
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