去甲斑螯素诱导的PP2A的抑制对提高CNE1的放射活性的影响

Research of Protein Phosphatase 2A Inhibition by Norcantharidin on Radiosensitivity Enhancement of Nasopharyngeal Carcinoma CNE1

目的研究去甲斑螯素所诱导的蛋白磷酸酶2A(PP2A)的抑制对鼻咽癌细胞系CNE1及其裸鼠移植瘤放射增敏的影响。方法采用免疫共沉淀、流式细胞术等方法探讨去甲斑螯素(40μmol·L^(-1))或(和)放射处理(8 Gy)对鼻咽癌细胞CNE1及其裸鼠移植瘤PP2A活性、细胞周期、凋亡的影响情况,研究去甲斑螯素抑制PP2A后于放射作用下所诱导的鼻咽癌细胞CNE1及其移植瘤组织生物学现象的变化。结果去甲斑螯素协同放射处理相比较其他各处理组,G2/M期细胞显著聚集增多(45.71±2.015)%,凋亡率也明显提高(75.63±6.11)%,裸鼠移植瘤抑瘤率达到87.64%。结论 PP2 A的抑制显著诱导鼻炎癌细胞的凋亡与延迟移植瘤的生长,其很有可能成为提高鼻咽癌放射增敏作用的新靶点。

OBJECTIVE To investigate the radiosensitizing effect of PP2A inhibition on nasopharyngeal carcinoma cells and its xenografts. METHODS Co-immunoprecipitation and flow cytometry were used to examine PP2A activity, cell cycle analysis and apoptosis of CNE1 and its xenografts, in order to explore the effect of radiosensitization in CNE1 cells. RE- SULTS Cell cycle distribution and apoptosis were measured by flow cytometry 24 h after treatment. The combination of 8 Gy and 40 μmol · L-1 norcantharidin produced significantly accumulation of cells in G2/M-phase （45.71± 2.015 ） % and more apoptosis（75.63 ±6. 11 ） % in CNE1 cell lines compared with norcantharidin alone and to radiation alone, norcanthari- din in combination with radiation produced the greatest effects on tumor growth slowing and decreasing tumor weight by 87.64% relative to vehicle in CNE1 xenografts. Our data demonstrate that inhibition of PP2A with radiation significantly sen- sitizes nasopharyngeal carcinoma cell lines in vitro and in vivo. CONCLUSION The inhibition of PP2A with norcantharidin inhibited xenograft growth obviously. Our results support further exploration of PP2A inhibition as part of radiotherapy regimens for NPC and potentially other solid tumors.