PTD-CHMP1A融合蛋白抑制肾细胞癌细胞的恶性生物学行为  

Recombinant protein PTD-CHMP1A inhibits malignant biological behavior of renal cell carcinoma cells

作　　者：由振强[1] 李丽丽[2] 张升[1] 谢锋[1] 杨林 郑高利[1] 辛艳飞[1] 

机构地区：[1]浙江省医学科学院安全性评价研究中心,浙江杭州310013 [2]浙江工业大学长三角绿色制药协同创新中心,浙江杭州310014

出　　处：《中国肿瘤生物治疗杂志》2018年第1期51-55,共5页Chinese Journal of Cancer Biotherapy

基　　金：浙江省自然科学基金资助项目(No.LQY18H160001;No.LY13H160031)~~

摘　　要：目的:探讨蛋白转导域(protein transduction domain,PTD)-染色质修饰蛋白1A(chromatin modifying protein 1A,CHMP1A)融合蛋白对肾细胞癌(renal cell carcenoma,RCC)细胞增殖、迁移、侵袭及体内移植瘤生长的影响。方法:分别用1、5、20μg/ml的PTD-CHMP1A(PTD-CHMP1A组)、5μg/ml的野生型CHMP1A(CHMP1A组)和PBS(PBS组)处理RCC细胞株A498和786-0。用MTT法检测PTD-CHMP1A对A498细胞增殖能力的影响,划痕愈合实验检测PTD-CHMP1A对A498细胞迁移能力的影响,用Transwell侵袭实验检测PTD-CHMP1A对A498和786-0细胞的侵袭能力的影响。将5×105个/ml的A498细胞注射于裸鼠体内,构建RCC移植瘤模型,观察20μg的PTD-CHMP1A对移植瘤生长的影响。结果:与CHMP1A和PBS组比较,1、5和20μg/ml的PTD-CHMP1A对A498细胞的增殖均出现不同程度的抑制作用,且呈明显的剂量和时间相关性;5μg/ml的PTDCHMP1A可有效抑制A498细胞的迁移(P<0.01)、A498和786-0细胞的侵袭能力(均P<0.05),且抑制A498细胞的侵袭能力呈剂量相关性。PTD-CHMP1A在体内可有效抑制裸鼠体内移植瘤的生长。结论:PTD-CHMP1A融合蛋白可以有效抑制RCC细胞的增殖、迁移、侵袭能力和体内移植瘤的生长。Objective： To study the influence of PTD-CHMP1A （protein transduction domain-chromatin modifying protein 1A） fusion proteins on proliferation, migration and invasion of renal cell carcinoma （RCC） cells in vitro and the growth of transplanted tumor in vi- vo. Methods： RCC A498 and 786-0 cells were treated with PTD-CHMP1A （1, 5, and 20 μg/ml）, CHMP1A （5 μg/ml） and PBS respec- tively. The effect of PTD-CHMP 1A on the proliferation of A498 cells was detected by MTT assay. The effect of PTD-CHMP 1A on the migration ofA498 cells was detected by scratch assay. The effect of PTD-CHMP1A on the invasion ability ofA498 and 786-0 ceils was detected by Transwell invasion assay. Finally, the transplanted tumor models were constructed by injecting 5 × 10^5 A498 cells into nude mice, and the effect of 20 μg PTD-CHMP1A on tumor growth was observed. Results： Compared with CHMP1A and PBS groups, PTD- CHMP1A fusion proteins （1, 5, and 20 μg/ml） showed a significantly restrained effect on the proliferation ofA498 tumor ceils, which was in dose-dependent and time-dependent manners. 5 -tg/ml of PTD-CHMP1A fusion proteins could effectively inhibit the migration ofA498 cells （P〈0.01 compared with CHMP1A group）, and the invasion of A498 and 786-0 cells （compared with ChmplA group, P〈 0.05）, besides, PTD-CHMP1A inhibited the invasion of A498 cells in a dose-dependent manner. Furthermore, PTD-CHMP1A could also observably inhibit tumor growth in vivo. Conclusion： PTD-CHMP1A fusion proteins effectively inhibited the proliferation, migration and invasion of RCC cells and the growth of transplanted tumor.

关 键 词：肾细胞癌 染色质修饰蛋白1A 蛋白转导域 侵袭 迁移 移植瘤模型 

分 类 号：R737.11[医药卫生—肿瘤] R730.2[医药卫生—临床医学]