Thoracic Surgery Department, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
Thoracic Surgery Department, The Affiliated Hospital of Qingdao University, Qingdao, China.
J Investig Med. 2019 Feb;67(2):338-345. doi: 10.1136/jim-2018-000839. Epub 2018 Oct 26.
Previous studies have demonstrated that CXCL12/CXCR4 axis is closely related to tumors such as malignant pleural mesothelioma (MPM). This research was conducted in order to detect whether CXCL12/CXCR4 inhibitors could restrain MPM and have a synergistic effect with chemotherapy, also to investigate the relationship of CXCL12/CXCR4 with other gene expressions in MPM. Forty mice were injected MPM cells and randomly divided into four groups: the PBS (control group), AMD3100 (CXCR4-CXCL12 antagonist), pemetrexed and AMD3100 plus pemetrexed. The mice were treated respectively for duration of 3 weeks. The size, bioluminescence and weight of tumors were measured. The differences between gene expressions in each group were analyzed. The tumor weights of each treatment group were lower than that of the control group (p<0.05). The bioluminescence of the tumor of the AMD3100 treatment group and the AMD3100 plus pemetrexed treatment group were lower than that of the control group (p<0.05), and AMD3100 was shown to have synergistic effects with pemetrexed (p<0.05). Among the 2.5 billion genes, several hundreds of genes expressed differently between groups. Results show that AMD3100 and pemetrexed can inhibit the growth of MPM in vivo, also that there is a better result if both are used together. Our findings suggest that CXCL12/CXCR4 axis affects a certain amount of gene expression in MPM.
先前的研究表明，CXCL12/CXCR4 轴与恶性胸膜间皮瘤（MPM）等肿瘤密切相关。本研究旨在检测 CXCL12/CXCR4 抑制剂是否能抑制 MPM 并与化疗产生协同作用，还研究了 CXCL12/CXCR4 与 MPM 中其他基因表达的关系。将 40 只小鼠注射 MPM 细胞，并随机分为四组：PBS（对照组）、AMD3100（CXCR4-CXCL12 拮抗剂）、培美曲塞和 AMD3100 加培美曲塞。各组分别治疗 3 周。测量肿瘤的大小、生物发光和重量。分析每组基因表达的差异。与对照组相比，各治疗组的肿瘤重量均较低（p<0.05）。AMD3100 治疗组和 AMD3100 加培美曲塞治疗组的肿瘤生物发光均低于对照组（p<0.05），且 AMD3100 与培美曲塞具有协同作用（p<0.05）。在 25 亿个基因中，有数百个基因在组间表达不同。结果表明，AMD3100 和培美曲塞均可抑制 MPM 的体内生长，两者联合使用效果更佳。我们的研究结果表明，CXCL12/CXCR4 轴影响 MPM 中一定数量的基因表达。
