人PSP94与TNFα衍生物联合治疗人前列腺癌的实验研究

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

Experiment Research on Human Prostate Carcinoma Therapy by Combination of Human PSP94 and TNFα Derivative

Recombinant eukaryotic plasimids pcDNA PSP94,pcDNA TNFα D11a and pcDNA PSP94 TNFα D11a respectively expressing human PSP94,TNFα D11a and PSP94 TNFαD11a bifunctional protein were constructed and injected into nude mouse model carrying human prostate carcinoma transplant,and at the same time PSP94,TNFα D11a proteins were also used to do this experiment research on human prostate carcinoma therapy by combination of human PSP94 and TNFα derivative.When the diameter of mouse tumor was up to 10 mm,the above three recombinant eukaryotic plasmids of 50 μg/mouse were injected into the left and right musculi quadriceps femoris of the mice in the different gorups,meanwhile mice injected with pcDNA3.0 vector were used as control group;rhPSP94 of 50 μg/kg,rhTNFαD11a of 10 6 U/kg and combination of them were administered one time per day respectively by muscular injection for ten days,the positive and negtive control groups were injected using cyclophosphamide and physiological sodium chloride respectively. The therapy effect was observed and the tumor inhibitory rate was calculated after killing the animals of gene therapy groups on the 15th day after administering and the animals of protein therapy groups on the 2nd day after stopping administering.The results indicated that in both gene and protein therapy groups,tumor of animals treated with PSP94 did not diminish,but necrosis and liquescence of different degrees were found in tumor tissue;tumor inhibition effect was not found in the groups treated with TNFα D11a;tumor of animals treated with PSP94 TNFα D11a fusion gene or combination of rhPSP94 and rhTNFα D11a not only diminished,but also had the phenomina of necrosis and liquescence of different degrees.The conclusions are as follows:(1)PSP94 has antitumor effect on prostate carcinoma in some degree;(2)PSP94 and TNF have the cooperation effect on prostate carcinoma.