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背景与目的 T肽是Tuftsin的衍生物,其基本功能是刺激巨噬细胞,提高巨噬细胞吞噬及分泌能力,通过增强效应细胞的细胞杀伤作用而被广泛用于多种恶性肿瘤术后抗肿瘤治疗。本研究旨在探讨T肽与化疗药物顺铂的联合能否提高铂类药物的抗肿瘤疗效及机制。方法应用酶联免疫吸附剂测定(enzyme-linked immunosorbent assay,ELISA)T肽和/或顺铂处理人巨噬细胞株U937后肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)和干扰素-γ(interferon-γ,IFN-γ)分泌水平的变化;应用裸鼠荷瘤动物模型,分析T肽和/或顺铂处理小鼠肿瘤变化情况以及小鼠用药期间外周血中巨噬细胞变化情况。结果 (1)应用ELISA检测发现在T肽组和T肽联合顺铂组中,U937细胞培养液中TNF-α水平明显高于对照组和顺铂组;T肽联合顺铂组中IFN-γ水平明显高于对照组、顺铂组和T肽组;(2)在小鼠荷瘤模型中,T肽联合顺铂组的肿瘤体积明显小于对照组、顺铂组和T肽组,并且小鼠没有明显的体重下降;(3)在小鼠外周血的检测分析中发现,T肽联合顺铂组中活化巨噬细胞数呈现增长趋势。免疫组化分析各组中肿瘤组织Ki67显示T肽联合顺铂组抑制肿瘤细胞增殖。结论 T肽能够促进巨噬细胞增殖和促进其分泌肿瘤细胞杀伤因子(TNF-α、IFN-γ);在体内动物模型中,T肽能够提高化疗药物如顺铂的疗效,使联合组具有更强的肿瘤抑制作用,同时能够减轻化疗药物的毒副作用。
Background and objective T-peptide is a derivative of Tuftsin. Its basic function is to stimulate macrophages and enhance phagocytosis and secretion of macrophages. It is widely used in anti-tumor of various malignancies after cell killing by enhancing effector cells treatment. The purpose of this study was to investigate whether the combination of T-peptide and chemotherapeutic drug cisplatin can improve the anti-tumor efficacy and mechanism of platinum-based drugs. Methods Tumor necrosis factor-α (TNF-α) and interferon-γ (TNF-α) were detected by enzyme-linked immunosorbent assay (ELISA) T peptide and / or cisplatin in human macrophage cell line U937 (IFN-γ, IFN-γ) secretion levels of mice; nude mice bearing tumor model, analysis of T-peptide and / or cisplatin treatment of tumor changes in mice and mice during the treatment of macrophages in peripheral blood Changes. Results (1) The level of TNF-α in U937 cell culture medium was significantly higher than that in control group and cisplatin group in T-peptide group and T-peptide combined with cisplatin group by ELISA test; IFN-γ in T peptide group and cisplatin group (2) In the tumor-bearing mouse model, the tumor volume of T-peptide plus cisplatin group was significantly smaller than that of control group, cisplatin group and T-peptide group (3) In the detection and analysis of mouse peripheral blood, it was found that the number of activated macrophages in T-peptide combined with cisplatin showed an increasing trend. Immunohistochemical analysis of Ki67 in each group showed that T-peptide plus cisplatin inhibited tumor cell proliferation. Conclusion T-peptide can promote macrophage proliferation and promote the secretion of tumor cell killer (TNF-α, IFN-γ). In in vivo animal model, T-peptide can improve the curative effect of chemotherapy drugs such as cisplatin, Strong tumor suppression, while reducing the toxic side effects of chemotherapy drugs.