PDTC合并泰素帝对裸鼠移植瘤抑制效应的研究

目的研究PDTC合并泰素帝对SGC-7901人胃癌细胞裸鼠移植瘤的抑制效应及对核因子-κB表达的影响,探讨其对泰素帝的化疗增敏作用。方法将接种SGC-7901人胃癌细胞成瘤的裸鼠分为PDTC组、泰素帝组、联合用药组及对照组,动态观察裸鼠移植瘤体积变化,采用实时荧光定量PCR法测定裸鼠移植瘤组织内c-IAP2及XIAP mRNA表达的改变,采用Western Blot方法检测NF-κB P65、I-κB蛋白表达的改变。结果治疗结束后所有药物治疗组瘤体体积均较对照组降低（P〈0.01）,联合用药组与PDTC组及泰素帝组相比,降低最为明显（P〈0.01）。泰素帝组XIAP及c-IAP2 mRNA表达较对照组升高（P〈0.05）,而联合用药组XIAP及c-IAP2 mRNA表达较对照组、泰素帝组明显下降（P〈0.01）。泰素帝处理后胞浆及胞核NF-κB P65含量增加,而PDTC联合作用后胞浆及胞核NF-κB P65含量较泰素帝组明显降低。结论泰素帝与PDTC均能抑制裸鼠移植瘤生长,并且两者具有协同作用,其机制可能与PDTC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。

The inhibitory effects of PDTC combined with taxotere on xenografted human gastric cancer in nude mice

Objective To investigate the inhibitory effects of pyrrolidine dithiocarbamate（PDTC）combined with taxotere on xenografted SGC-7901 human gastric cancer in nude mice.Methods Human gastric cancer SGC-7901 cells were inoculated in nude mice.The nude mice were divided into 4 groups：the PDTC group（treated with PDTC）,the taxotere group（treated with PDTC）,the combination group（treated with PDTC and taxotere） and the control group（no treatment）.The volumes of the transplanted tumors were monitored during the treatment,and the tumor tissues were collected at the end of the treatments.The expressions of c-IAP2 and XIAP mRNA were detected by real-time PCR;and the expressions of NF-κB P65 and I-κB proteins were measured by Western Blot method.Results At the end of treatment tumor volumes in all drug treatment groups were smaller than that in control group（P 0.01）,the tumor volumes in combined treatment group were decreased most compared to taxotere and PDTC groups（P 0.01）.The expressions of XIAP and c-IAP2 mRNA increased in taxotere group,and decreased in combination group compared tothe control group（P 0.01）.The cytoplasmic and nucleus NF-κB P65 contents were increased after taxotere treatment,but significantly decreased after combination administration with PDTC.Conclusion Both docetaxel and PDTC can inhibit the growth of xenografted human gastric cancer in nude mice,and they have synergistic effect,which may be associated with inhibition of docetaxel-induced activation of NF-κB by PDTC,resulting in inhibiting the apoptosis-related gene expression.