P162对食管癌细胞株Eca109的放射增敏作用及其对p75NTR表达的影响

 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、10 μmol/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5 μmol/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。

Enhancement of radiosensitivity and inhibition of p75NTR expression in esophageal cancer cell line Eca109 by a novel peptide P162 targeting to G3BP

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 neurotrophin receptor (p75NTR) 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 Eca109 cells were observed under inverted microscope. The expression of surface marker p75NTR in human esophageal cancer stem cells was analyzed by flow cytometry. RESULTS：The peptide P162 inhibited Eca109 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 p75NTR was increased. Compared with simple irradiation group, the expression level of p75NTR was obviously decreased in P162 treatment group. CONCLUSION：The peptide P162 increases the radiosensitivity of esophageal cancer cell line Eca109, and inhibits the expression of p75NTR in esophageal cancer stem cells. This sensitization effect may be related to inhibition of esophageal cancer stem cells.