Shock wave permeabilization with ribosome inactivating proteins: a new approach to tumor therapy.
Shock wave permeabilization with ribosome inactivating proteins: a new approach to tumor therapy.
复制标题
使用核糖体失活蛋白进行冲击波透化：肿瘤治疗的新方法。
作者：
M. Delius;Gerhard Adams
体外冲击波是临床上用于碎石术的微秒级高压脉冲。最近，冲击波被证明会引起细胞膜渗透性的瞬时增加。因此，我们假设，冲击波可能能够转移到肿瘤细胞的肿瘤杀伤剂，并在体外和体内检查。体外实验中，将核糖体失活蛋白gelonin和saporin分别转染L1210、SSK 2和HeLa细胞，建立了剂量-反应曲线。通过3-（4，5-二甲基噻唑-2-基）-2，5-二苯基四唑溴化物测定法评估使细胞增殖降低50%的药物浓度（IC 50），并计算来自冲击波应用的增强因子。发现冲击波增强白树素的作用，从L1210细胞中的900倍增强到HeLa细胞中的40，000倍，并且增强皂草素的作用，从L1210细胞中的300倍增强到HeLa细胞中的15，000倍。在体内，在鼠肿瘤模型中评估白树素和皂草素的作用。在腹膜内施用白树素或皂草素后，用冲击波处理C3 H小鼠中局部生长的SSK 2纤维肉瘤肿瘤。冲击波的应用延迟了肿瘤的生长，并且在40%的动物中诱导了持续>180天的长期缓解。总之，冲击波增强了核糖体失活蛋白的作用，并导致肿瘤完全缓解。通过冲击波将有毒物质局部转移到肿瘤中构成了局部治疗肿瘤的新途径。
Extracorporeal shock waves are high-pressure pulses of microsecond duration clinically used for lithotripsy. Recently, shock waves been shown to cause a transient increase of the permeability of the cell membrane. We therefore hypothesized that shock waves might be able to transfer tumoricidal agents into tumor cells and examined this in vitro and in vivo. In vitro, the ribosome inactivating proteins gelonin and saporin were transferred into L1210, SSK2, and HeLa cells, and dose-response curves were established. The drug concentration that reduced the cell proliferation by 50% (IC50) was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and the enhancement factors from shock wave application were calculated. It was found that shock waves enhanced the action of gelonin from 900-fold in L1210 cells to 40,000-fold in HeLa cells and the action of saporin from 300-fold in L1210 cells to 15,000-fold in HeLa cells. In vivo, the effect of gelonin and saporin was assessed in a murine tumor model. SSK2 fibrosarcoma tumors locally grown in C3H mice were treated with shock waves after i.p. administration of gelonin or saporin. Shock wave application delayed the tumor growth, and long-term remissions lasting >180 days were induced in 40% of the animals. In conclusion, shock waves enhanced the action of ribosome inactivating proteins and led to complete tumor remissions. The local transfer of toxic substances by shock waves into tumors constitutes a new approach to a local tumor therapy.
免疫毒素生物学和治疗进展：第四届国际免疫毒素研讨会摘要。
影响因子：
11.2
作者：
Frankel,AE;FitzGerald,D;Siegall,C;Press,OW
通讯作者：
Press,OW