CXCL13激活Akt促进肺癌放疗抵抗

耿闪闪; 何翠; 陈春丽; 邓鑫州; 邱力; 柯青; 吴林; 段奇文; 施明亮; 骆志国

doi:10.3971/j.issn.1000-8578.2020.19.0491

CXCL13激活Akt促进肺癌放疗抵抗

CXCL13 Activates Akt to Promote Radioresistance of Lung Cancer

摘要

摘要:
目的探讨CXCL13在肺癌放疗抵抗中的作用及分子机制。
方法利用公共数据库分析了CXCL13和CXCR5在肺癌组织中的表达水平, 及其表达水平与放疗患者预后的关系。Western blot检测不同浓度CXCL13和Akt抑制剂LY294002对人肺癌H1975细胞Akt表达活化的影响; CCK-8法、流式细胞术和克隆形成实验检测CXCL13和LY294002对辐射处理后H1975细胞增殖、凋亡、克隆形成能力的影响。
结果肺癌组织中CXCL13和其受体CXCR5表达水平明显高于正常组(P<0.003), CXCL13高表达与患者不良进展后生存期(PPS)密切相关。100 ng∕ml CXCL13处理辐射后的H1975细胞, 细胞增殖水平显著高于对照组(P=0.015), 细胞凋亡水平显著低于对照组(P=0.001), 细胞克隆形成能力显著高于对照组(P=0.014); 100 ng∕ml CXCL13显著激活Akt; 8 Gy辐射处理后, 20 μg/ml的LY294002联合CXCL13处理组的细胞增殖水平显著低于CLCX13单独处理组(P=0.019), 细胞凋亡水平显著高于CLCX13单独处理组(P=0.003), 20 μg/ml的LY294002联合CXCL13处理组的细胞克隆形成能力显著低于CLCX13单独处理组(P=0.001)。
结论 CXCL13通过激活Akt介导肺癌放疗抵抗。

Abstract:
Objective To investigate the role and molecular mechanism of CXCL13 on the radioresistance of lung cancer.
Methods Public database was used to analyze the expression levels of CXCL13 and CXCR5 in lung cancer patients, and the relation between the expression levels of CXCL13/CXCR5 and the prognosis of lung cancer patients who received radiotherapy only. Western blot was used to detect the effects of different concentrations of CXCL13 and Akt inhibitor LY294002 on Akt expression and activation in human lung cancer H1975 cells. CCK-8 method, flow cytometry and clone formation assay were used to analyze the effect of CXCL13 and LY294002 on the proliferation, apoptosis and cell clone formation ability after X ray radiation treatment, respectively.
Results The expression levels of CXCL13 and its receptor CXCR5 in lung cancer patients were significantly higher than those in the normal group (P < 0.003). The high expression level of CXCL13 is closely related to the progression of postnatal survival (PPS) of lung cancer patients. H1975 cells treated with 100ng/ml CXCL13 showed significantly higher proliferation level (P=0.015) and clone formation ability (P=0.014), but lower apoptosis level (P=0.001) than the control group. 100ng/ml CXCL13 significantly activated Akt. After 8Gy X-ray radiation treatment, the cell proliferation level (P=0.019) and clone formation ability (P=0.001) in the 20μg/ml LY294002 combined with CXCL13 group were significantly lower than those in the CXCL13 group alone, while the apoptosis level in the combination group was significantly higher than that in the CXCL13 group alone (P=0.003).
Conclusion CXCL13 promotes the radioresistance of lung cancer by activating Akt.

HTML全文

参考文献(23)

施引文献

资源附件(0)