摘要
目的:研究靶向Ras-GTP酶激活蛋白SH3功能区结合蛋白(G3BP)的新药P162对人食管癌细胞株Eca109的放射增敏作用及其对p75神经营养因子受体(p75NTR)表达的影响。方法:CCK-8法检测P162对食管癌细胞株Eca109增殖抑制的影响;集落形成实验检测P162对Eca109细胞的放射增敏效应,单击多靶模型拟合细胞存活曲线并计算放射增敏比;倒置显微镜观察细胞形态学改变;流式细胞术检测p75NTR的表达。结果:P162对食管癌细胞株Eca109有增殖抑制作用,且呈时间和剂量依赖性,2.5、5.0、10μmol/L P162对Eca109细胞的放射增敏比分别为1.54、2.35和2.33。随着照射剂量的增加,食管癌细胞中p75NTR的表达增加,经5μmol/L P162处理的实验组中p75NTR的表达明显低于未经处理的对照组。结论:P162对Eca109细胞有放射增敏作用,并且能抑制食管癌干细胞p75NTR的表达。P162的增敏作用可能与抑制食管癌干细胞有关。
AIM： To investigate the effect of a novel peptide P162 targeting to Ras-GTPase-activating protein SH3 domain-binding protein （G3BP） on the radiosensitivity of esophageal cancer cells and the expression of p75 neurotro- phin receptor （p75^NTR） in esophageal cancer stem cells. METHODS： The proliferation inhibitory rate was measured by CCK-8 assay. Colony formation assay was performed to determine the radiosensitizing effect of P162 on Eca-109 cell line. Single-hit multitarget mode was used to plot survival curves. The morphological changes of Eeal09 ceils were observed un- der inverted microscope. The expression of surface marker p75^NTR in human esophageal cancer stem cells was analyzed by flow cytometry. RESULTS： The peptide P162 inhibited Ecal09 cell proliferation in a time- and dose-dependent manner. The radiosensitization enhancement ratios （ SERDq ） of P162 at concentrations of 2.5, 5.0 and 10 μmol/L were 1.54, 2.35 and 2.33, respectively. With the increase in the irradiation dose, the expression level of surface marker p75^NTR was in- creased. Compared with simple irradiation group, the expression level of p75^NTR was obviously decreased in P162 treatment group. CONCLUSION： The peptide P162 increases the radiosensitivity of esophageal cancer cell line Ecal09, and inhib- its the expression of p75^NTR in esophageal cancer stem cells. This sensitization effect may be related to inhibition of esopha- geal cancer stem cells.
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2013年第1期103-107,共5页
Chinese Journal of Pathophysiology
基金
湖北省自然科学基金资助项目(No.2010CDB03505)
