四川九章生物科技有限公司與中國(guó)醫(yī)科院藥物研究所（隸屬于中國(guó)醫(yī)學(xué)科學(xué)院；學(xué)術(shù)和職稱系統(tǒng)歸北京協(xié)和醫(yī)學(xué)院，是國(guó)家重點(diǎn)藥物研究機(jī)構(gòu)）建立了戰(zhàn)略性技術(shù)研發(fā)合作關(guān)系，共同成立了“綠原酸合作開發(fā)項(xiàng)目委員會(huì)”，共同進(jìn)行綠原酸的藥理機(jī)制研究，促進(jìn)基礎(chǔ)研究成果向臨床應(yīng)用的轉(zhuǎn)化。   

2017年1月上旬，中國(guó)醫(yī)科院藥物研究所聯(lián)合四川九章生物科技有限公司及北京世紀(jì)壇醫(yī)院腦膠質(zhì)瘤科在《Scientific Reports》 上發(fā)布了名為《Chlorogenic acid inhibits glioblastomagrowth through repolarizating macrophage from M2 to M1 phenotype》（綠原酸通過(guò)復(fù)極化使M2型巨噬細(xì)胞轉(zhuǎn)化為M1型巨噬細(xì)胞抑制惡性膠質(zhì)瘤細(xì)胞的生長(zhǎng)）的文章，詳細(xì)闡述并論證了注射用綠原酸（四川九章生物科技有限公司研發(fā)）促進(jìn)惡性腫瘤細(xì)胞凋亡和抑制腫瘤生長(zhǎng)的機(jī)制，即通過(guò)復(fù)極化上調(diào)腫瘤相關(guān)巨噬細(xì)胞M1表型，抑制腫瘤相關(guān)巨噬細(xì)胞M2表型，同時(shí)促進(jìn)M2型巨噬細(xì)胞向M1型巨噬細(xì)胞的轉(zhuǎn)化。

該項(xiàng)研究成果有望引領(lǐng)全球小分子免疫天然藥物作用機(jī)制的探索方向，開創(chuàng)惡性膠質(zhì)瘤治療的新紀(jì)元。

Abstract

     Glioblastoma is an aggressive tumor that is associated with distinctive infiltrating microglia/macrophages populations. Previous studies demonstrated that chlorogenic acid (5caffeoylquinic acid, CHA), a phenolic compound with low molecular weight, has an anti-tumor effect in multiple malignanttumors. In the present study, we focused on the macrophage polarization to investigate the molecular mechanisms behind the anti glioma response ofCHA in vitro and in vivo. We found that CHA treatment increased the expression of M1 markers induced by LPS/IFNγ, including iNOS, MHC II (I-A/I-Esubregions) and CD11c, and reduced the expression of M2 markers Arg and CD206 induced by IL-4, resulting in promoting the production of apoptoticlike cancer cells and inhibiting the growth of tumor cells by co-culture experiments. The activations of STAT1 and STAT6, which are two crucial signaling events in M1 and M2polarization, were significantly promoted and suppressed by CHA in macrophages, respectively. Furthermore, In G422 xenograft mice, CHA increased the proportion of CD11c-positive M1 macrophages and decreased the distribution of CD206-positive M2 macrophages in tumor tissue, consistent with the reduction of tumor weight observed in CHA-treated mice. Overall these findings indicated CHA as a potential therapeuticapproach to reduce glioma growth through promoting M1-polarized macrophage and inhibiting M2 phenotypic macrophage.

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