PO.TB10.16 · 肿瘤生物学
葡萄籽原花青素提取物与水飞蓟水飞蓟素提取物的联合应用可累加性地减少THP-1来源的M2巨噬细胞向肺肿瘤微环境的募集
Combinations of grape seed procyanidin extract and milk thistle silymarin extract additively decrease recruitment of THP-1 derived M2 macrophages into the lung tumor microenvironment.
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摘要 Abstract
中文摘要
引言:葡萄籽原花青素提取物(GSE)和水飞蓟水飞蓟素提取物(MTE)分别作为促进心血管和肝胆健康的保健食品补充剂被广泛使用。GSE和MTE均含有高水平的结构上各异的多酚,且每种药剂均已被证明对肺癌发挥抗肿瘤作用。此前我们已表明,GSE与MTE的联合应用降低了肺癌细胞对促肿瘤、促M2巨噬细胞极化的CCL2趋化因子的产生。CCL2是肿瘤微环境中的一种关键趋化因子,可促进巨噬细胞的募集及向促肿瘤M2c表型的极化,通过营造促肿瘤环境而促进肿瘤进展。用GSE+MTE靶向肺肿瘤微环境中的募集和M2c巨噬细胞极化,可能代表一种针对肺癌的新型免疫治疗策略。
方法:将THP-1细胞用佛波醇-12-肉豆蔻酸酯-13-乙酸酯(PMA)分化为M0细胞,再按此前所述用白细胞介素(IL)-10启动分化为M2c巨噬细胞。随后使用CD163和CD206引物通过qPCR分析确认M2c表型。采用THP-1来源的M0和M2c巨噬细胞与A549细胞及条件化细胞培养上清液的共培养迁移/侵袭实验(模拟肺肿瘤微环境),评估GSE和MTE单独或联合条件化处理对A549细胞募集M2c细胞能力的影响。
结果:用GSE和MTE对A549细胞进行条件化处理,累加性地减少了A549细胞对CCL2的产生,且与经GSE+MTE条件化处理的A549细胞/上清液共培养累加性地降低了M2c细胞的迁移/侵袭。
结论:在本研究中,我们报道了GSE和MTE在降低肺肿瘤微环境中促肿瘤M2c细胞迁移/侵袭方面的累加效应。我们的发现阐明了GSE联合MTE抗肺癌的一种潜在的新型免疫调节机制,并支持继续研究该联合方案用于肺癌的预防和治疗。
查看英文原文 English abstract
Introduction : Grape seed procyanidin extract (GSE) and milk thistle silymarin extract (MTE) are widely used as health food supplements to promote cardiovascular and hepatobiliary health, respectively. Both GSE and MTE contain high levels of structurally distinct polyphenols and each agent has been shown to exert antineoplastic effects against lung cancer. Previously we have shown that the combinations of GSE and MTE decreased production of the tumor promoting, M2 macrophage polarizing CCL2 chemokine by lung cancer cells. CCL2 is a key chemokine in the tumor microenvironment that facilitates recruitment and polarization of macrophages toward the tumor promoting M2c phenotype, which promotes tumor progression by creating a pro-tumorigenic environment. Targeting recruitment to and M2c macrophage polarization in the lung tumor microenvironment with GSE + MTE may represent a novel immunotherapeutic strategy against lung cancer.
Methods :THP-1 cells were differentiated into M0 cells with phorbol-12-myristate-13-acetate (PMA), then to M2c macrophages using interleukin (IL)-10 priming as previously described. M2c phenotype was then confirmed using qPCR profiling with CD163 and CD206 primers. The effects of GSE and MTE conditioning, alone or in combination, on the ability of A549 cells to recruit M2c cells were assessed using co-culture migration/invasion assay of THP-1 derived M0 and M2c macrophages with A549 cells and conditioned cell culture supernatants, simulating the lung tumor microenvironment.
Results : Conditioning of A549 cells with GSE and MTE additively reduced CCL2 production by A549 cells and co-culture with GSE + MTE conditioned A549 cells/supernatants additively decreased migration/invasion of M2c cells.
Conclusion s: In the present study, we report on the additive effects of GSE and MTE on reducing the migration/invasion of tumor promoting M2c cells in the lung tumor microenvironment. Our findings illustrate a potential novel immunomodulatory mechanism of GSE combined with MTE against lung cancer and support the continued investigation of the combinations for lung cancer prevention and treatment.
利益披露 Disclosure
J. T. Mao, None..
D. Oliva, None..
J. Schilter, None..
L. Rollin, None..
L. Jih, None.