Department of Interventional Vascular Surgery, The First Affiliated Hospital of Yangtze University, Jingzhou, China.
Kaohsiung J Med Sci. 2022 Aug;38(8):781-789. doi: 10.1002/kjm2.12540. Epub 2022 Apr 25.
This study aims to discover the therapeutic effect of chemokine (CXC motif) receptor 4 (CXCR4) antagonist AMD3100 combined with transcatheter arterial chemoembolization (TACE) in a rat model with hepatocellular carcinoma (HCC). An orthotopic model of HCC was established and treated with TACE (doxorubicin-lipiodol emulsion) with or without AMD3100. The tumor volume was measured by magnetic resonance imaging (MRI). Histopathological changes were detected by hematoxylin-eosin (HE) staining. HCC cell apoptosis was assessed by terminal deoxyribonucleotidyl transferase (TdT)-mediated biotin-16-dUTP nick-end labeling (TUNEL) staining. Immunohistochemistry was used to detect the expression of CD34, hypoxia-inducible factor 1α (HIF-1α), vascular endothelial growth factor (VEGF), and Ki67. Gene and protein expressions were quantified by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and western blotting, respectively. Both TACE and AMD3100 reduced the tumor volume in orthotopic rat model of HCC with the decreased CXCR4 expression in tumor tissues, and the combination had better effect. However, TACE increased the microvessel density (MVD) in HCC tissues of rats, while AMD3100 treatment reduced MVD in HCC tissues. AMD3100 reduced the TACE induced MVD in HCC tissues with the reduction of HIF-1α and VEGF expression. Either AMD3100 or TACE could promote HCC cell apoptosis accompanying by decreased cell proliferation, and their combined use had better therapeutic effects. CXCR4 antagonist AMD3100 enhance therapeutic efficacy of TACE in rats with HCC via promoting the HCC cell apoptosis, reducing cell proliferation, and inhibiting MVD, thus reducing tumor volume.
本研究旨在探讨趋化因子（CXC 基序）受体 4（CXCR4）拮抗剂 AMD3100 联合经导管动脉化疗栓塞（TACE）治疗肝癌（HCC）大鼠模型的疗效。建立 HCC 原位模型，并采用 TACE（阿霉素-碘油乳剂）联合或不联合 AMD3100 进行治疗。通过磁共振成像（MRI）测量肿瘤体积。苏木精-伊红（HE）染色检测组织病理学变化。末端脱氧核苷酸转移酶（TdT）介导的生物素-16-dUTP 缺口末端标记（TUNEL）染色评估 HCC 细胞凋亡。免疫组织化学检测 CD34、缺氧诱导因子 1α（HIF-1α）、血管内皮生长因子（VEGF）和 Ki67 的表达。通过定量逆转录聚合酶链反应（qRT-PCR）和蛋白质印迹法分别定量检测基因和蛋白质表达。TACE 和 AMD3100 均降低了 HCC 原位大鼠模型的肿瘤体积，同时降低了肿瘤组织中 CXCR4 的表达，联合治疗效果更好。然而，TACE 增加了 HCC 组织中的微血管密度（MVD），而 AMD3100 治疗则降低了 HCC 组织中的 MVD。AMD3100 降低了 TACE 诱导的 HCC 组织中 MVD 的表达，同时降低了 HIF-1α 和 VEGF 的表达。AMD3100 或 TACE 均可促进 HCC 细胞凋亡，同时降低细胞增殖，联合使用具有更好的治疗效果。CXCR4 拮抗剂 AMD3100 通过促进 HCC 细胞凋亡、降低细胞增殖和抑制 MVD，从而降低肿瘤体积，增强 HCC 大鼠 TACE 的治疗效果。
