埃及眼镜蛇粗毒素对癌症微环境免疫的调节作用

IF 0.7 Q4 PHARMACOLOGY & PHARMACY Egyptian Pharmaceutical Journal Pub Date : 2023-04-01 DOI:10.4103/epj.epj_156_22
Hosni Neweigy, M. Gouida, M.E. El nagger, Mohamed Y. Salem
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引用次数: 0

摘要

癌症可以通过激活调节性T细胞来控制免疫系统的抑制机制;髓源性抑制细胞(MDSCs)和增加共抑制剂蛋白的表达。蛇毒通过靶向特定的分子途径显示出抗癌活性。目的研究不同剂量埃及眼镜蛇毒液与顺铂对健康和肿瘤小鼠的免疫调节作用。材料与方法2 ~ 3月龄Balb/c雌性小鼠分为对照组、实性(皮下)肿瘤组和软性(埃利希腹水)肿瘤组。小鼠分别皮下和腹腔注射含有2×106和1.5×106细胞的埃利希腹水癌细胞28天和10天。结果顺铂组MDSCs减少,1/10、1/30 LD50组MDSCs减少,1/30 LD50组MDSCs减少,差异均无统计学意义(P=0.055)。1/20 LD50治疗组、实体瘤治疗组和腹水肿瘤治疗组的调节性T细胞在顺铂和1/20 LD50治疗组中均无显著升高,而在顺铂和1/30 LD50治疗组中,对照组调节性T细胞显著降低,在1/20和1/10 LD50治疗组中,调节性T细胞无显著升高。实体瘤组T regs升高,但各实体瘤治疗组T regs升高,1/20 LD50联合顺铂治疗腹水瘤组T regs升高无统计学意义。结论低剂量蛇毒可使肿瘤微环境中MDSCs和T细胞减少,高剂量可使肿瘤微环境中MDSCs和T细胞增加,有待进一步研究。
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Cancer micro-environment immune modulation by Egyptian cobra (Naja haje) crud venom
Background Cancer can control immune system suppression mechanisms by activating regulatory T cells; myeloid-derived suppressor cells (MDSCs) and increasing the expression of co-inhibitor proteins. Snake venoms showed anticancer activity by targeting specific molecular pathways. Objective Here, we investigate the immunomodulatory effects of Egyptian cobra (Naja haje) venom different doses compared with cisplatin in healthy and cancer murine models. Materials and methods Female Balb/c mice aged 2–3 months, are separated into three general groups (control groups, solid (subcutaneous) tumors, and soft (ehrlich ascites) tumors. Mice were inoculated with ehrlich ascites carcinoma cells about 2×106 and 1.5×106 cells subcutaneously and intraperitoneal for 28 and 10 days, respectively. Results MDSCs decreased nonsignificantly in control groups treated with cisplatin, 1/10, 1/30 LD50 also, in ascites tumor group treated with 1/30 LD50 (P=0.055). While it increased non-significantly in healthy control treated with 1/20 LD50, all treated solid tumor groups and in ascites tumor groups treated with cisplatin and 1/20 LD50, on the other hand, Regulatory T cells in control groups decreased significantly in groups treated with cisplatin and 1/30 LD50 on the other hand it increased nonsignificantly in groups treated with 1/20 and 1/10 LD50. In solid tumor groups, T regs increased with no statistical significance in all treated solid tumor groups also, in ascites tumor groups treated with 1/20 LD50 and cisplatin. Conclusion Low doses of (Naja haje) crud venom reduce MDSCs and T reg in the microenvironment of tumor while higher doses increase them, further investigation will be needed.
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来源期刊
Egyptian Pharmaceutical Journal
Egyptian Pharmaceutical Journal PHARMACOLOGY & PHARMACY-
CiteScore
1.10
自引率
0.00%
发文量
37
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