Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, 110029, India.
Ann Hematol. 2013 Jan;92(1):101-9. doi: 10.1007/s00277-012-1572-5. Epub 2012 Sep 13.
Multiple myeloma (MM) is classically illustrated by a desynchronized cytokine system with rise in inflammatory cytokines. There are recent reports which emphasized the potential role of angiogenesis in the development of MM. Role of cyclooxygenase 2 (COX-2) is well documented in the pathogenesis of solid tumors, but little is known about its occurrence and function in hematologic neoplasms. Involvement of neoangiogenesis is reported in the progression of MM, and angiopoietins probably contribute to this progression by enhancing neovascularization. Circulatory and mRNA levels of angiogenic factors and cyclooxygenase were determined in 125 subjects (75 MM patients and 50 healthy controls) by using enzyme-linked immunosorbent assay and quantitative PCR. We observed significant increase for angiogenic factors (Ang-1, Ang-2, hepatocyte growth factor, and vascular endothelial growth factor) and cyclooxygenase at circulatory level, as well as at mRNA level, as compared to healthy controls except insignificant increase for Ang-1 at circulatory level. We have also observed the significant positive correlation of all angiogenic factors with cyclooxygenase. The strong association found between angiogenic factors and COX-2 in this study may lead to the development of combination therapeutic strategy to treat MM. Therefore, targeting COX-2 by using its effective inhibitors demonstrating antiangiogenic and antitumor effects could be used as a new therapeutic approach for treatment of MM.
多发性骨髓瘤(MM)的特征是细胞因子系统失调,炎症细胞因子升高。最近有报道强调了血管生成在 MM 发展中的潜在作用。环氧化酶 2(COX-2)在实体肿瘤的发病机制中作用明确,但在血液恶性肿瘤中其发生和功能知之甚少。新血管生成在 MM 的进展中被报道,血管生成素可能通过增强新血管生成来促进这一进展。通过酶联免疫吸附试验和定量 PCR,在 125 名受试者(75 名 MM 患者和 50 名健康对照者)中测定了血管生成因子和环氧化酶的循环和 mRNA 水平。与健康对照组相比,我们观察到循环和 mRNA 水平的血管生成因子(Ang-1、Ang-2、肝细胞生长因子和血管内皮生长因子)和环氧化酶显著增加,除了循环水平的 Ang-1 增加不显著。我们还观察到所有血管生成因子与环氧化酶呈显著正相关。本研究中发现的血管生成因子与 COX-2 之间的强关联可能导致联合治疗策略的发展,以治疗 MM。因此,通过使用具有抗血管生成和抗肿瘤作用的有效抑制剂靶向 COX-2 ,可以作为治疗 MM 的新治疗方法。