TNFα及PDTC诱导雄激素非依赖性前列腺癌细胞凋亡的实验研究  

The Experimental Study in Apoptosis of Androgen Independent Prostate Cancer Cells Induced by TNF and PDTC

作　　者：林大春[1] 单玉喜[2] 张顺兴[1] 

机构地区：[1]镇江市第一人民医院,江苏镇江212002 [2]苏州大学附属第二医院,苏州215004

出　　处：《苏州大学学报（医学版）》2002年第5期510-512,共3页Suzhou University Journal of Medical Science

摘　　要：目的　探讨雄激素非依赖性前列腺癌治疗的新途径。方法　以含 2 0 %小牛血清的RPMI - 16 4 0为培养基 ,在 37℃、5 %CO2 培养箱中孵育雄激素非依赖性前列腺癌细胞株 (PC - 3) ,倍增至所需的细胞数后 ,行SCID鼠右腋皮下接种 ,建立雄激素非依赖性前列腺癌动物模型。待瘤体长至约 1.0cm3 大小时 ,随机分成 4组 :A组 (对照组 ) ,皮下注射生理盐水每只 0 .2ml;B组瘤体内注射TNFα(2 0 0 μg/kg体重 ) ;C组腹腔注射PDTC(2 0 0mg/kg体重 ) ;D组同时注射TNFα及PDTC(剂量同B、C组 )。隔日 1次 ,2 8d后取出瘤体 ,进行瘤体大小及细胞凋亡的检测。结果　各用药组瘤体大小及凋亡率与对照组相比有显著性差异 (P <0 .0 1) ,B组抑瘤率为 70 .9% ,C组为4 5 .9% ,D组为 89.5 %。用药前后的瘤重相比 ,D组有显著性差异 (P <0 .0 1) ,B、C组无显著性差异 (P >0 .0 5 )。在治疗过程中 ,对照组死亡 1只 ,用药组无死亡。结论　TNFα、PDTC对雄激素非依赖性前列腺癌细胞的生长均有抑制作用 ,TNFα联合PDTC可显著缩小瘤体大小 ,其作用机制可能为 :TNFα诱导PC - 3细胞的凋亡 ,PDTC对TNFα的诱导起增强作用。Objective To investigate novel therapeutic strategies for androgen independent prostate cancer. Methods Human AIPC cell line PC-3 were routinely propagated in monolayer culture in a humidified incubator at 37℃ in a 5%CO 2,95% air atmosphere. Cells were grown in RPMI-1640 medium supplemented with 20% heat-inactivated bobby calf serum. When the cell number was enough, SCID mice were injected subcutaneously with PC-3 cells (2.0×10 6 cells/mouse in 0.2ml of 0.9%NaCl) harvested by quick trypsinization of ongoing culture. Then the SCID mice were raised in SPF grade room. The SCID mice were divided at random into four groups after a palpable primary tumor was present. Control mice received 0.9%NaCl subcutaneously (0.2ml/mouse). TNFα was injected in tumor for group B(200μg/kg). C group was injected intraperitoneally with PDTC(200mg/kg).D group received TNFα and PDTC in the same way. Therapy was administered qod. Solid tumors were taken out and measured with dial caliper and then the obtained tumors were fixed for apoptosis assay after 28 days. Results The therapeutic groups compared with the control showed significant difference in size and the percentage of apoptotic cells ( P <0.01) and the tumor inhibition rate was 70.9%(B group), 45.9%(C group), and 89.5%(D group). The tumor volume was significantly smaller after therapy than that before therapy in D group ( P <0.01) which was not shown in B group or C group however ( P >0.05). In the course of therapy, one mouse died in the control group.Conclusions The growth of androgen independent prostate cancer cells were significantly inhibited by TNFα or PDTC. But the more significant therapeutic efficiency is detected by the combination of TNFα and PDTC. It indicates that the mechanism underlying TNFα growth inhibition in PC-3 cells, whose growth is androgen independent, is to induce apoptotic cell death and PDTC enhances the ability of TNFα.

关 键 词：TNFΑ PDTC 诱导 雄激素非依赖性前列腺癌 细胞凋亡 实验研究 

分 类 号：R737.25[医药卫生—肿瘤]