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目的观察携带NDRG2基因的腺病毒(Ad-NDRG2)与重组人肿瘤坏死因子相关凋亡诱导配体(rhTRAIL)联合给药对人前列腺癌细胞株PC-3的抗肿瘤增效作用。方法以Ad-NDRG2感染体外培养的PC-3细胞,采用Western blot方法检测NDRG2蛋白表达水平的变化。流式细胞仪检测术和MTT实验分析Ad-NDRG2给药后PC-3细胞对TRAIL敏感性的变化。建立裸鼠移植瘤模型,观察Ad-NDRG2与TRAIL联合给药的体内抗肿瘤作用。结果病毒感染单位为40MOI时的感染效率可达100%。Ad-NDRG2感染后PC-3细胞中NDRG2和p21蛋白表达明显增加,而CyclinD1表达减少。Ad-NDRG2协同浓度10-7ng/ml以上rhTRAIL作用48 h,可增强对PC-3细胞的生长抑制作用(抑制率≥37.5%)和诱导凋亡作用(凋亡率≥35.4%)。动物实验表明:rhTRAIL组,Ad-NDRG2组,Ad-NDRG2与rhTRAIL联合给药组移植瘤的抑瘤率分别为32.6%、30.1%和54.7%,两药相互作用指数CDI为0.86。结论腺病毒介导NDRG2基因感染细胞后,可增强人前列腺癌PC-3细胞在体内及体外对rhTRAIL的敏感性。
Objective To observe the antitumor effect of adenovirus carrying NDRG2 gene (Ad-NDRG2) and recombinant human tumor necrosis factor-related apoptosis-inducing ligand (rhTRAIL) on prostate cancer cell line PC-3. Methods Ad-NDRG2 was used to infect PC-3 cells cultured in vitro. The expression of NDRG2 protein was detected by Western blot. Flow cytometry and MTT assay were used to analyze the sensitivity of PC-3 cells to TRAIL after Ad-NDRG2 administration. A nude mouse xenograft model was established to observe the antitumor effect of Ad-NDRG2 combined with TRAIL in vivo. Results The infection rate of virus infected unit was 40% at 100%. After Ad-NDRG2 infection, the expression of NDRG2 and p21 in PC-3 cells increased significantly, while the expression of CyclinD1 decreased. Ad-NDRG2 could enhance the growth inhibition of PC-3 cells (inhibitory rate≥37.5%) and induce apoptosis (apoptosis rate≥35.4%) after treated with rhTRAIL over 10-7ng / ml for 48h. Animal experiments showed that the tumor inhibition rates of rhTRAIL group, Ad-NDRG2 group and Ad-NDRG2 combined with rhTRAIL group were 32.6%, 30.1% and 54.7% respectively, and the CDI of the two drugs was 0.86. Conclusion Adenovirus-mediated NDRG2 gene-infected cells can enhance the sensitivity of human prostate cancer PC-3 cells to rhTRAIL in vivo and in vitro.