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、20 μg/ml 的PTD-CHMP1A（PTD-CHMP1A组）、5 μg/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20 μg 的PTD-CHMP1A对移植瘤生长的影响。结果：与CHMP1A和PBS组比较，1、5 和20 μg/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；5 μg/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 vivo.Methods: RCC A498 and 786-0 cells were treated with PTD-CHMP1A (1, 5, and 20 μg/ml), CHMP1A (5 μg/ml) and PBS respectively.The effect of PTD-CHMP1A on the proliferation of A498 cells was detected by MTT assay. The effect of PTD-CHMP1A on the migration of A498 cells was detected by scratch assay. The effect of PTD-CHMP1A on the invasion ability of A498 and 786-0 cells was detected by Transwell invasion assay. Finally, the transplanted tumor models were constructed by injecting 5×105 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, PTDCHMP1A fusion proteins (1, 5, and 20 μg/ml) showed a significantly restrained effect on the proliferation of A498 tumor cells, which was in dose-dependent and time-dependent manners. 5 μg/ml of PTD-CHMP1A fusion proteins could effectively inhibit the migration of A498 cells (P<0.01 compared with CHMP1A group), and the invasion of A498 and 786-0 cells (compared with Chmp1A 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.

浙江省自然科学基金资助项目（No. LQY18H160001, No. LY13H160031）