TRAIL联合PDTC对SGC-7901细胞生长抑制和凋亡诱导的实验研究  

An experimental study of the effect of TRAIL combined with PDTC on the growth inhibition and apoptosis induction of SGC-7901 gastric cancer cells

作　　者：刘玲[1] 费素娟[1] 

机构地区：[1]徐州医学院附属医院消化内科,江苏徐州221002

出　　处：《徐州医学院学报》2009年第11期718-721,共4页Acta Academiae Medicinae Xuzhou

摘　　要：目的观察肿瘤坏死因子相关凋亡诱导配体(TRAIL)及TRAIL联合核转录因子核因子-κB(NF-κB)活性特异性抑制剂吡咯烷二硫代氨基甲酸盐(PDTC)对胃癌细胞SGC-7901的生长抑制和凋亡诱导作用,并寻找逆转TRAIL耐药的方法。方法采用不同浓度的TRAIL及TRAIL联合PDTC作用于胃癌细胞后,MTT法检测细胞生长抑制率,流式细胞仪检测细胞的凋亡率,免疫细胞化学染色方法观察药物作用前后NF-κB表达情况。结果单独使用TRAIL时,随着浓度从50μg/L增加到500μg/L,细胞的生长抑制率和凋亡率逐渐增加(P<0.05),但这种作用是非线性的。TRAIL联合0.05μmol/L、0.1μmol/L PDTC后肿瘤细胞的生长抑制率和凋亡率较单用TRAIL显著下降(P<0.05);而联合1μmol/L、10μmol/L PDTC后其作用较上有所上升(P<0.05)。联合作用组p65蛋白在胞核中染色的强度低于单纯使用TRAIL组(P<0.05)。结论TRAIL对胃癌细胞株SGC-7901具有一定程度的生长抑制和凋亡诱导作用;NF-κB信号转导途径可能具有双向调节作用,大剂量PDTC可能逆转胃癌细胞对TRAIL的耐药。Objective To observe the effect of a combination of pyrrolidine dithiocarbonate （PDTC）, a specific inhibitor of NF-κB and tumor necrosis factor （TNF） -related apoptosis- inducing ligand （TRAIL） on the apoptosis of gastric cancer cells and their effect on the expression of NF -κB, and to search for the approaches to reversing resistance to TRAIL in human stomach cancer ceils. Methods Various concentrations of TRAIL and PDTC were added in exponential growth SGC - 7901 gastric cancer cells. MTT assays were used to measure the growth inhibitory effect of combined use of TRAIL and PDTC or alone. Apoptosis of gastric cancer cell SGC - 7901 was analyzed with PI staining method and flow cytometry （FCM）. The expression of NF -κB was observed using immunohistochemical staining method. Results After the SGC - 7901 gastric cancer cells were exposed to TRAIL at a dose of 50 μg/L to 500 μg/L, the growth inhibitory rate and apoptosis rate increased （P 〈 0.05 ）, but there was no linearity for this dose - effect relationship. Following TRAIL treatment in combination with 0.05 μmol/L and 0.1 μmol/L PDTC, the growth inhibitory rate of and apoptosis rate significantly decreased compared with treatment with TRAIL or PDTC alone （ P 〈 0.05 ） , while following TRAIL treatment in combination with PDTC 1 μmol/L and 10 μmol/L, the growth inhibitory rate and apoptosis rates increased compared with treatment with TRAIL or PDTC alone （P 〈 0.05 ）. The two drugs presented synergistic or added effect on SGC- 7901 cells. The expression of NF- κB decreased subsequent to the treatment of PDTC（ P 〈 0.05）. Conclusion TRAIL has the effect of growth inhibition and apoptosis induction on SGC - 7901 gastric cells to some degree. The NF - κB signal pathway might have a bidirectional effect in apoptosis regulation, and large dose of PDTC could reduce the resistance of TRAIL in SGC -7901 gastric cells.

关 键 词：肿瘤坏死因子相关凋亡诱导配体 吡咯烷二硫代氨基甲酸盐 胃癌细胞 凋亡 核因子-κB 

分 类 号：R735.2[医药卫生—肿瘤]