刚地弓形虫抗肿瘤作用及其机制研究进展

doi:10.12140/j.issn.1000-7423.2020.04.017

摘要/Abstract

摘要：

刚地弓形虫是一种重要的机会致病性原虫,严重威胁着人类健康,但弓形虫虫体、培养上清/排泄分泌抗原、裂解抗原、分泌蛋白均被证实具有显著的抗肿瘤作用。其中,诱导肿瘤细胞凋亡、抑制肿瘤组织新生血管生成以及增强宿主自身免疫细胞功能的机制在弓形虫抗肿瘤过程中发挥着关键作用。本文综述了弓形虫抗肿瘤作用的研究进展,以及虫体及其相关组分抗肿瘤作用的相关机制。

关键词: 刚地弓形虫, 抗肿瘤, 癌症治疗, 效应成分

Abstract:

Toxoplasma gondii is an important opportunistic pathogenic protozoan and is a big threat to human health. However, studies have revealed significant anti-tumor effects of the T. gondii parasite, as well as its culture supernatant or excretory secretory antigen, antigen lysate, and secreted proteins. In the mechanism of the anti-tumor effects, the induction of tumor cell apoptosis, inhibition of tumor tissue neovascularization and enhancement of the function of host immune cells play crucial roles. In this review, we summarize research progress on the anti-tumor effects of T. gondii and the mechanisms in association with the parasite and its related components.

Key words: Toxoplasma gondii, Anti-tumor effect, Cancer treatment, Effector component

中图分类号:

R382.5

张富强, 乔姣姣, 李浩然, 张振超, 李祥瑞, 王帅. 刚地弓形虫抗肿瘤作用及其机制研究进展[J]. 中国寄生虫学与寄生虫病杂志, 2020, 38(4): 496-502.

ZHANG Fu-qiang, QIAO Jiao-jiao, LI Hao-ran, ZHANG Zhen-chao, LI Xiang-rui, WANG Shuai. Research progress on the anti-tumor effects of Toxoplasma gondii and the underlying mechanisms[J]. Chinese Journal of Parasitology and Parasitic Diseases, 2020, 38(4): 496-502.

图/表 1

表1

刚地弓形虫抗肿瘤作用及其相关机制

效应成分	体内/外	相关肿瘤	相关机制	参考文献
虫体
RH株	体内	小鼠结肠癌ct26	抑制肿瘤组织微血管的生成	11
		小鼠B16黑色素瘤	提高CD3⁺、CD4⁺、CD8⁺、NK细胞杀伤活性	12
	体外	小鼠结肠癌ct26	诱导细胞发生 G2/M 期阻滞	9
		人白血病HPB-ALL细胞、人鼻咽癌CNE-2Z细胞、乳腺癌MCF-7细胞、前列腺癌DU-145细胞、食管癌EC-109细胞	不明	13,15
		人白血病细胞K562和肺癌A549 细胞	调控P53和Bcl-2基因表达水平	14-15
Pru株	体内	小鼠B16黑色素瘤	降低肿瘤组织血管内皮生长因子VEGF的表达水平	16
Me49株	体内	B16F10黑色素瘤	抑制肿瘤新生血管的生成	17
		Lewis肺癌（LLC）	抑制肿瘤新生血管的生成	18
cps株	体内	B16F10黑色素瘤	CD8+T细胞数量及活性明显提高	5,21
		ID8DV卵巢癌	CD8⁺T细胞免疫活性增强、CD45⁺CD3⁺CD4⁺Foxp3⁺调节性T细胞百分比下降	6,21
		胰腺癌	IL-12和IFN-γ的产生以及MyD88信号的转导	7,22
培养上清/排泄分泌抗原
培养上清	体外	卵巢癌SKOV-3细胞	通过线粒体凋亡途径诱导卵巢癌SKOV-3细胞凋亡	8,23
		乳腺癌MCF-7细胞、人结肠癌sw480细胞	诱导MCF-7细胞凋亡	24-25
		肺癌A549细胞、白血病细胞THP-1	调控细胞周期蛋白cyclinB1和cdc2的表达水平,诱导癌细胞凋亡	26-28
		胃癌细胞株SGC-7901和BGC-823 细胞	调控凋亡蛋白（Bax、p53和Bcl-2）的表达水平诱导癌细胞凋亡	29-30
		肝癌HepG2细胞	上调细胞内钙离子浓度、Caspase-3表达水平	31
排泄分泌抗原（ESA）	体内	小鼠B16F10黑色素瘤、小鼠Lewis 肺癌	降低CD4⁺CD25⁺Foxp3⁺T（Treg）细胞比例	32-33
		小鼠B16F10黑色素瘤	提高NK细胞、CD8⁺T细胞数量及杀伤功能	34-35
裂解抗原（TLA）
TLA	体外	人脑胶质瘤U373MG和U87MG细胞	抑制胶质瘤细胞的增殖和迁移	36
	体内	人脑胶质瘤U373MG和U87MG细胞	抑制人类恶性胶质瘤的生长	36
		小鼠恶性肉瘤细胞Sarcoma 180	降低CD31(肿瘤组织中的血管生成标志物)的表达水平	37
		结肠癌ct26细胞	降低血清转移标志物TIMP-1的表达水平、IL-12的表达水平升高、骨髓源性巨噬细胞中MyD88信号通路的表达增强	38
		纤维肉瘤（WEHI 164）和结肠癌（CT26）、B16F10黑色素瘤	树突状细胞（DC）经TLA诱导成熟后可以通过特异性免疫反应发挥抑癌作用	39-40
分泌蛋白
ROP16	体外	肝癌HepG2细胞	调控凋亡相关蛋白caspase9、 Bax、 Bcl2的表达水平	43
GRA15II	体外	肝癌Hepa1-6细胞	诱导巨噬细胞向M1极化、下调基质金属蛋白酶-9（MMP-9）和MMP-2的表达	44

表1

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