Badr Gamal, Sayed Eman Abdo, Abdel-Ghaffar Wafaa H, Badr Badr M, Sayed Leila H, Sayed Aml, Mahmoud Mohamed H, Alamery Salman
Zoology Department, Faculty of Science, Assiut University, 71516 Assiut, Egypt.
Laboratory of Immunology, Zoology Department, Faculty of Science, Assiut University, 71516 Assiut, Egypt.
Saudi J Biol Sci. 2021 Apr;28(4):2374-2380. doi: 10.1016/j.sjbs.2021.01.034. Epub 2021 Jan 28.
Treating drug-resistant cancer cells is a clinical challenge and it is also vital to screen for new cancer drugs. Multiple myeloma (MM) is a plasma cell clonal cancer that, despite many experimental therapeutics, remains incurable. In this study, two MM cell line lines U266 and RPMI 8226 were used to determine the impact of camel whey protein (CWP). The CWP IC was calculated by MTT examination, while the flow cytometry analysis was used to investigate the chemotaxis responses of MM cells in relation to CXCL12 and the pro-apoptotic effect of CHP. MM cells were treated with CWP and Western blot analysis was used to determine the underlying molecular mechanisms. Dose and time based on the impact of CWP on the cell viability of MM cells with IC of 50 μg/ml, without affecting the viability of normal healthy PBMCs. CWP reduced chemotaxis of MM cells significantly from the CXC chemokine ligand 12 (CXCL12). Using Western blot analysis, we found that CWP decreased the activation of AKT, mTOR, PLCβ3, NFαB and ERK, which was mechanistically mediated by CXCL12/CXCR4. In both U266 and RPMI 8226, CWP induced apoptosis by upregulating cytochrome expression. In addition, CWP mediated the growth arrest of MM cells by robustly decreasing the expression of the anti-apoptotic Bcl-2 family members Bcl-2, Bcl-XL and Mcl-1. Conversely, the expression of pro-apoptotic Bcl-2 family members Bak, Bax and Bim was increased after treatment with CWP. Our data indicates CWP's therapeutic potential for MM cells.
治疗耐药癌细胞是一项临床挑战，筛选新型抗癌药物也至关重要。多发性骨髓瘤（MM）是一种浆细胞克隆性癌症，尽管有许多实验性治疗方法，但仍然无法治愈。在本研究中，使用了两种MM细胞系U266和RPMI 8226来确定骆驼乳清蛋白（CWP）的影响。通过MTT检测计算CWP的IC，同时使用流式细胞术分析来研究MM细胞对CXCL12的趋化反应以及CWP的促凋亡作用。用CWP处理MM细胞，并使用蛋白质印迹分析来确定潜在的分子机制。基于CWP对IC为50μg/ml的MM细胞活力的影响确定剂量和时间，且不影响正常健康外周血单个核细胞（PBMC）的活力。CWP显著降低了MM细胞对CXC趋化因子配体12（CXCL12）的趋化性。通过蛋白质印迹分析，我们发现CWP降低了AKT、mTOR、PLCβ3、NFαB和ERK的激活，这是由CXCL12/CXCR4机制介导的。在U266和RPMI 8226中，CWP通过上调细胞色素表达诱导凋亡。此外，CWP通过显著降低抗凋亡Bcl-2家族成员Bcl-2、Bcl-XL和Mcl-1的表达介导MM细胞的生长停滞。相反，在用CWP处理后，促凋亡Bcl-2家族成员Bak、Bax和Bim的表达增加。我们的数据表明CWP对MM细胞具有治疗潜力。
