The contribution of angiogenesis inhibitor TNP- 4 70 to the growth and m etastasis of ACHN renal cell carcinom a (RCC) was studied. TNP- 4 70 (40 m g/ kg,every two days) was ad- ministrated to BABL / c nude m ice be...The contribution of angiogenesis inhibitor TNP- 4 70 to the growth and m etastasis of ACHN renal cell carcinom a (RCC) was studied. TNP- 4 70 (40 m g/ kg,every two days) was ad- ministrated to BABL / c nude m ice bearing ACHN RCC. The mice were sacrificed after a treatment duration of 31days and the weight and volum e of subcutaneous tum ors as well as foci of lung m etastasis were m easured.The microvascular density(MVD) of the tumor as well as the PCNA index and apoptotic index of the tum or cells were evaluated imm unohistochem ically. Result showed that the growth of ACHN RCC was suppressed significantly and none metastasis was ob- served in TNP- 4 70 - treated m ice. Compared with the control group,the MVD was decreased m arkedly (P<0 .0 1) and the apoptotic index was increased significantly (P<0 .0 1) in the treated group. The tumor volume was positively correlated to the MVD (r=0 .714 4 ,P<0 .0 1) and in- versely correlated to the apoptotic index(r=- 0 .86 0 7,P<0 .0 1) ,and MVD was conversely cor- related to the apoptotic index.It was determ ined that TNP- 4 70 could effectively inhibit angiogene- sis of ACHN RCC,which resulting in ischemia and hypoxia,leading to increased apoptosis,thus obviously suppressing the growth and metastasis of ACHN RCC in nude m ice.展开更多
目的探讨环氧化酶-2(cyclooxygenase-2,COX-2)抑制剂联合白细胞介素-2(interleukin-2,IL-2)对小鼠肾癌免疫治疗的作用及其机制。方法以Renca细胞建立Babl/c小鼠异位肾癌模型,共28只,随机等分成4组,不同组别予以不同给药,分别为IL-2组、N...目的探讨环氧化酶-2(cyclooxygenase-2,COX-2)抑制剂联合白细胞介素-2(interleukin-2,IL-2)对小鼠肾癌免疫治疗的作用及其机制。方法以Renca细胞建立Babl/c小鼠异位肾癌模型,共28只,随机等分成4组,不同组别予以不同给药,分别为IL-2组、NS-398(一种COX-2抑制剂)组、IL-2+NS-398组和空白对照组。在第14天、28天提取各组荷瘤小鼠外周血,用流式细胞术检测调节性T细胞(regulatory T cells,Treg)的变化;切取荷瘤小鼠瘤体及脾脏,免疫组化检测小鼠脾脏和肿瘤局部Treg的变化。结果小鼠异位肾癌在不同药物处理后,肿瘤体积出现明显变化,联合用药组肿瘤体积减小明显,经多组t检验,与其他组相比差异有统计学意义(P<0.05)。同时,COX-2抑制剂能下调荷瘤小鼠外周血、肿瘤及脾脏中Treg的表达,且与IL-2联合有协同作用(P<0.05)。结论 COX-2抑制剂联合IL-2可显著抑制荷瘤小鼠异位肾癌的发展,说明Treg的下调是抑制肾癌生长的可能机制之一。展开更多
文摘The contribution of angiogenesis inhibitor TNP- 4 70 to the growth and m etastasis of ACHN renal cell carcinom a (RCC) was studied. TNP- 4 70 (40 m g/ kg,every two days) was ad- ministrated to BABL / c nude m ice bearing ACHN RCC. The mice were sacrificed after a treatment duration of 31days and the weight and volum e of subcutaneous tum ors as well as foci of lung m etastasis were m easured.The microvascular density(MVD) of the tumor as well as the PCNA index and apoptotic index of the tum or cells were evaluated imm unohistochem ically. Result showed that the growth of ACHN RCC was suppressed significantly and none metastasis was ob- served in TNP- 4 70 - treated m ice. Compared with the control group,the MVD was decreased m arkedly (P<0 .0 1) and the apoptotic index was increased significantly (P<0 .0 1) in the treated group. The tumor volume was positively correlated to the MVD (r=0 .714 4 ,P<0 .0 1) and in- versely correlated to the apoptotic index(r=- 0 .86 0 7,P<0 .0 1) ,and MVD was conversely cor- related to the apoptotic index.It was determ ined that TNP- 4 70 could effectively inhibit angiogene- sis of ACHN RCC,which resulting in ischemia and hypoxia,leading to increased apoptosis,thus obviously suppressing the growth and metastasis of ACHN RCC in nude m ice.
文摘目的探讨环氧化酶-2(cyclooxygenase-2,COX-2)抑制剂联合白细胞介素-2(interleukin-2,IL-2)对小鼠肾癌免疫治疗的作用及其机制。方法以Renca细胞建立Babl/c小鼠异位肾癌模型,共28只,随机等分成4组,不同组别予以不同给药,分别为IL-2组、NS-398(一种COX-2抑制剂)组、IL-2+NS-398组和空白对照组。在第14天、28天提取各组荷瘤小鼠外周血,用流式细胞术检测调节性T细胞(regulatory T cells,Treg)的变化;切取荷瘤小鼠瘤体及脾脏,免疫组化检测小鼠脾脏和肿瘤局部Treg的变化。结果小鼠异位肾癌在不同药物处理后,肿瘤体积出现明显变化,联合用药组肿瘤体积减小明显,经多组t检验,与其他组相比差异有统计学意义(P<0.05)。同时,COX-2抑制剂能下调荷瘤小鼠外周血、肿瘤及脾脏中Treg的表达,且与IL-2联合有协同作用(P<0.05)。结论 COX-2抑制剂联合IL-2可显著抑制荷瘤小鼠异位肾癌的发展,说明Treg的下调是抑制肾癌生长的可能机制之一。
