抑制SSRP1对胶质瘤细胞增殖、化疗敏感性的影响  

Effect of inhibition of SSRP1 on glioma cells proliferation and chemosensitivity to temozolomide

作　　者：陶祥[1] 张文斐[1] 冀保卫[1] 张戈 陈治标[1] TAO Xiang;ZHANG Wen-fei;JI Bao-wei;ZHANG Ge;CHEN Zhi-biao(Department of Neurosurgery,Renmin Hospital of Wuhan University,Wuhan 430060,China)

机构地区：[1]武汉大学人民医院神经外科,武汉430060

出　　处：《中国临床神经外科杂志》2022年第9期760-764,共5页Chinese Journal of Clinical Neurosurgery

摘　　要：目的 探讨结构特异性识别蛋白1(SSRP1)与胶质瘤预后的相关性,以及抑制SSRP1对胶质瘤细胞增殖及化疗敏感性的影响。方法 应用生信分析方法,检索中国胶质瘤数据库CGGA数据集,分析SSRP1表达与胶质瘤预后相关性。体外培养胶质瘤U251、U87细胞,应用CBL0137抑制SSRP1,应用替莫唑胺(TMZ)检测化疗敏感性。应用CCK8法检测细胞增殖,利用免疫印迹法检测MAPK信号通路(p-38、ERK及JNK)表达。结果 生信分析结果显示,胶质瘤SSRP1呈高表达,随胶质瘤级别增加,SSRP1表达明星上调(P<0.05);SSRP1高表达胶质瘤总生存期明显缩短(P<0.05)。抑制SSRP1,明显抑制体外培养U251、U87细胞增殖(P<0.05),增加U251、U87细胞对TMZ化疗敏感性(P<0.05),对U251、U87细胞p-38、ERK及JNK蛋白表达水平无明显影响,但明显降低U251、U87细胞p-38、ERK及JNK蛋白磷酸化水平(P<0.05)。结论 胶质瘤SSRP1呈高表达,与病人不良预后有关;抑制SSRP1,明显抑制胶质瘤细胞增殖,并增加其对TMZ的化疗敏感性,其机制可能与抑制MAPK信号通路有关。Objective To investigate the correlation between expression of structure specific recognition protein 1(SSRP1) and prognoses of glioma patients, and the effect of inhibiting SSRP1 on glioma cells proliferation and chemotherapy sensitivity to temozolomide(TMZ). Methods The CGGA dataset of China Glioma Database was serched and the correlation between SSRP1expression and prognosis of glioma patients was analyzed using bioinformatics analysis method. The U251 and U87 cells were cultured in vitro, CBL0137 was used to inhibit SSRP1, and TMZ was used to detect the sensitivity of chemotherapy. Cell proliferation was detected by CCK8 assay, and the expression of MAPK signaling pathway(p-38, ERK and JNK) was detected by Western blotting. Results The results of bioinformatics analysis showed that the expression of SSRP1 was high in glioma;the expression of SSRP1 was up-regulated with the increase of glioma grade(P<0.05);the overall survival time of glioma patients with high SSRP1 expression was significantly shorter than those with low SSRP1 expression(P<0.05). Inhibition of SSRP1 significantly inhibited the proliferation of U251 and U87cells in vitro(P<0.05), increased the sensitivity of U251 and U87 cells to TMZ chemotherapy(P<0.05), and had no significant effect on the protein expression levels of p-38, ERK and JNK in U251 and U87 cells(P>0.05). However, the phosphorylation levels of p-38, ERK and JNK protein in U251 and U87 cells were significantly decreased(P<0.05). Conclusions The high expression of SSRP1 in glioma is associated with poor prognosis. Inhibition of SSRP1 can significantly inhibit the proliferation of glioma cells and increase their sensitivity to TMZ chemotherapy, which may be related to the inhibition of MAPK signaling pathway.

关 键 词：胶质瘤 结构特异性识别蛋1(SSRP1) CBL0137 细胞增殖 U251细胞 U87细胞 化疗敏感性 预后 

分 类 号：R739.41[医药卫生—肿瘤]