Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.
Department of Neurology, David Geffen School of Medicine, University of California Los Angeles (UCLA), Los Angeles, CA, USA.
Mol Biol Rep. 2022 Jun;49(6):4161-4170. doi: 10.1007/s11033-022-07163-0. Epub 2022 May 24.
Vascular endothelial growth factor (VEGF) is one of the angiogenic mediators that can be secreted by leukemic cells and plays an important role in tumor invasion and metastasis. Another important agent contributing to the relapse of ALL is C-X-C chemokine receptor type-4 (CXCR-4), expression of this receptor in cancer cells has been related to metastasis. It has been identified that genistein-a soy-derived isoflavonoid-has anti-angiogenesis functions. We aimed to show the effects of this compound on VEGF and CXCR-4 in Acute lymphoblastic leukemia (ALL) cell models.
The cytotoxicity of Genistein was measured using the MTS colorimetric assay. After being treated with Genistein, the expression of VEGF in mRNA and protein levels was measured in MOLT-4 and Jurkat cells. We also used flow cytometry assay to determine the expression of CXCR-4 in cell surfaces. We found that Genistein decreased cell viability in two cell models while was more effective on MOLT-4 cells. After Genistein-treatment, surface expression levels of CXCR-4 were decreased, while VEGF secretion and mRNA expression levels were increased in MOLT-4 and Jurkat cells.
The results suggest that Genistein may not be a reliable choice for the treatment of ALL; however, this different identified pattern can be useful for the recognition of VEGF and CXCR-4 modulators and thus for planning new treatments for leukemia and other VEGF related disorders.
血管内皮生长因子（VEGF）是一种血管生成介质，可由白血病细胞分泌，并在肿瘤侵袭和转移中发挥重要作用。另一个导致 ALL 复发的重要因素是 C-X-C 趋化因子受体 4（CXCR-4），癌细胞中这种受体的表达与转移有关。已确定大豆异黄酮金雀异黄素具有抗血管生成功能。我们旨在展示该化合物对急性淋巴细胞白血病（ALL）细胞模型中 VEGF 和 CXCR-4 的影响。
使用 MTS 比色法测量金雀异黄素的细胞毒性。在用金雀异黄素处理后，测量 MOLT-4 和 Jurkat 细胞中 VEGF 的 mRNA 和蛋白水平表达。我们还使用流式细胞术测定细胞表面 CXCR-4 的表达。我们发现金雀异黄素在两种细胞模型中降低细胞活力，而对 MOLT-4 细胞更有效。金雀异黄素处理后，MOLT-4 和 Jurkat 细胞中 CXCR-4 的表面表达水平降低，而 VEGF 的分泌和 mRNA 表达水平增加。
结果表明，金雀异黄素可能不是 ALL 治疗的可靠选择；然而，这种不同的鉴定模式对于识别 VEGF 和 CXCR-4 调节剂可能很有用，从而为白血病和其他与 VEGF 相关的疾病的新治疗方法的制定提供了思路。
