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构建了表达人 PSP94、TNFα衍生物 ( TNFα D1 1 a)及 PSP94与 TNFα D1 1 a( PSP94- TNFαD1 1 a)双功能蛋白真核表达质粒 pc DNA- TNFα D1 1 a、pc DNA- PSP94和 pc DNA- PSP94- TNFαD1 1 a,与 rh PSP94和 rh TNFα D1 1 a蛋白分别在人前列腺癌裸鼠移植瘤动物模型上进行了 PSP94与 TNFαD1 1 a联合治疗人前列腺癌的实验研究 .当动物肿瘤直径长至约 1 0 mm时 ,将以上 3种真核表达质粒分别以 50 μg/只的量给相应组动物的左右四头肌内注射一次 ,同时设 pc DNA3.0空载体对照组 ;rh PSP9450μg/kg、rh TNFαD1 1 a 1 0 0万单位 /kg、rh PSP94和 rh TNFαD1 1 a以同样剂量联合给药 ,肌肉注射 ,每 d一次 ,连续 1 0 d,同时设环磷酰胺阳性对照组和生理盐水阴性对照组 .基因治疗动物给药后第 1 5d处死 ,蛋白治疗组停药后第 2 d处死 ,观察疗效 ,计算抑瘤率 .结果显示 ,以上述方式给药 ,无论是基因治疗组还是重组蛋白组 ,给 PSP94的动物肿瘤虽然未见明显缩小 ,但肿瘤组织均出现不同程度的坏死和液化现象 ;给 TNFαD1 1 a的未见明显的抑瘤效果 ;PSP94-TNFαD1 1 a融合基因或 rh PSP94+ rh TNFαD1 1 a联合给药 ,不仅肿瘤有所缩小 ,而且也有不同程度的坏死和液化现象出现 .初步认为 :( 1 ) PSP94有一定的抗前列腺
The recombinant plasmid pcDNA-TNFα D1 1 a, pc DNA-PSP94 and pcDNA-TNFα D1a were expressed in E.coli BL21 DNA-PSP94-TNFαD1 1 a, and rh PSP94 and rh TNFα D1 1 a protein in human prostate cancer xenografts in nude mice were used in the experimental study on the combination of PSP94 and TNFαD1 1 a in human prostate cancer.When the tumor diameter When the length was about 10 mm, the above three eukaryotic expression plasmids were respectively injected into the left and right quadriceps of the corresponding group at the dose of 50 μg / mouse, and the pcDNA3.0 empty vector control group was also set; rh PSP9450 μg / kg, rh TNFαD1 1 a 10 million units / kg, rh PSP94 and rh TNFαD1 1 a co-administered at the same dose, intramuscular injection, once a day for 10 consecutive days, the same set of cyclophosphamide positive control group and Saline control group.The gene therapy animals were sacrificed on the 15th day after drug administration, and the protein therapy group was sacrificed on the 2th day after stopping the treatment, the curative effect was observed and the tumor inhibition rate was calculated.The results showed that in the above manner, both the gene therapy group Or a recombinant protein group that gives tumors of PSP94 animals Although there was no obvious shrinkage, necrosis and liquefaction appeared in tumor tissues to varying degrees; no obvious tumor-inhibiting effect was observed on TNFαD1 1a; PSP94-TNFαD1 1 a fusion gene or rh PSP94 + rh TNFαD1 1 a combined administration, Not only the tumor has been reduced, but also have varying degrees of necrosis and liquefaction phenomenon.Preliminary that (1) PSP94 have a certain anti-prostate