Olive Leaf Extract Reduces Myeloid-Derived Suppressor Cells, and Modulates the Function of Residual Cells in Experimental Model of Melanoma

Mahboubeh Ashourpour, A. Namdar, N. Kheshtchin, Morteza Hafezi, Najmeh Khosravianfar, M. Ajami, B. Delfan, Yaser Azizi, S. Arab, R. Mirzaei, A. Mirshafiey, J. Hadjati, A. Razavi
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引用次数: 4

Abstract

Background: Immunosuppression in melanoma is mediated by increased accumulation of Myeloid Derived Suppressor Cells (MDSCs). Olive Leaf Extract (OLE) has been developed as a natural anti-inflammatory, anti-oxidant, anti-proliferative and antiapoptotic agent on cancer immunotherapy. Objective: To investigate whether OLE could inhibit MDSCs, enhance anti-tumor activities and consequently increase the survival rate of the murine melanoma model. Methods: The C57BL/6 mice were inoculated subcutaneously with B16/F10 melanoma tumor cell lines. Induced mice were orally treated with 500 mgkg-1 of olive extract per kg of body weight for 8 consecutive days. The frequency and function of MDSCs and induction of inflammatory mediators as well as tumor growth and survival rate were assessed in treated and untreated mice. Results: The results of current study revealed that the optimal dose of OLE (500 mgkg-1) reduced the tumor growth (40%), and prolonged mice survival (25%) by significant decreasing (P<0.05) the number (over 50%), and suppressive function of MDSCs (over 60%) (P<0.05). OLE was also significantly (P<0.05) down regulated the induction of inflammatory agents in melanoma-bearing mice (over 50%) at the applied dose (500 mgkg-1). Conclusion: Therefore, these results altogether provided some evidence that regulation of immunosuppression were the possible therapeutic effects of OLE in tumor cells.
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橄榄叶提取物减少髓源性抑制细胞,并调节黑色素瘤实验模型中残留细胞的功能
背景:黑色素瘤的免疫抑制是由髓源性抑制细胞(MDSCs)积累增加介导的。橄榄叶提取物(Olive Leaf Extract, OLE)作为一种天然抗炎、抗氧化、抗细胞增殖和抗细胞凋亡的肿瘤免疫治疗药物已被开发出来。目的:探讨OLE是否能抑制MDSCs,增强其抗肿瘤活性,从而提高小鼠黑色素瘤模型的存活率。方法:用B16/F10黑色素瘤细胞系皮下接种C57BL/6小鼠。以每公斤体重500 mg -1的橄榄提取物口服诱导小鼠,连续8天。在治疗和未治疗的小鼠中评估MDSCs的频率和功能、炎症介质的诱导以及肿瘤的生长和存活率。结果:本研究结果显示,OLE最佳剂量(500 mgkg-1)通过显著降低MDSCs数量(P<0.05以上)和抑制MDSCs功能(P<0.05以上),使肿瘤生长降低(40%),延长小鼠生存时间(25%)。在施加剂量(500 mgkg-1)时,OLE对荷瘤小鼠(50%以上)炎症因子的诱导作用也显著(P<0.05)下调。结论:综上所述,这些结果为OLE对肿瘤细胞免疫抑制的调节可能提供了一些证据。
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