Natural small molecule self-assembled hydrogel inhibited tumor growth and lung metastasis of 4T1 breast cancer by regulating the CXCL1/2-S100A8/9 axis
Natural small molecule self-assembled hydrogel inhibited tumor growth and lung metastasis of 4T1 breast cancer by regulating the CXCL1/2-S100A8/9 axis
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天然小分子自组装水凝胶通过调节CXCL1/2-S100A8/9轴抑制4T1乳腺癌肿瘤生长和肺转移
DOI：
10.1016/j.matdes.2022.111435
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发表时间：
2022-11
影响因子：
8.4
通讯作者：
Haimin Lei
中科院分区：
文献类型：
--
作者：
Yuqin Yang;Desheng Cai;Yisong Shu;Zhihua Yuan;Wenmin Pi;Yaozhi Zhang;Jihui Lu;Jingyi Jiao;Xuehao Cheng;Feifei Li;Penglong Wang;Haimin Lei
抑制肿瘤生长和远处转移是乳腺癌治疗的关键。然而，主要依靠手术、化疗和放疗的治疗方法远不能令人满意。已经证明CXCL1/2-S100A8/9轴在BC治疗中起重要作用。因此，我们构建了一种天然产物水凝胶，通过阻断CXCL1信号传导来治疗BC。GK-GA （genkwa Flos-glycyrrhizic acid的植物化学物质）水凝胶采用一步“绿色”方法设计。药效学研究表明，GK-GA具有显著的抗肿瘤和抗肺转移活性，当剂量为6.25 mg·kg−1时，对肿瘤生长的抑制率（IRG）超过90%，且无明显毒性。此外，有效的抗肿瘤效率也归因于聚集/组装诱导滞留（AIR）特性。RNA测序分析显示，GK-GA组BCL2、CASP3、CXCL1、CXCL2、CXCR2、S100A8、S100A9基因表达明显下调，western blot （WB）进一步证实了这一结果。我们的研究结果表明，天然产物GK-GA水凝胶通过BCL2-CASP3线粒体凋亡途径和CXCL1/2-S100A8/9途径抑制肿瘤生长和肺转移。这项研究为一步制备新的无赋形剂纳米分散体，无载体添加，无有机溶剂，“绿色”方法，特别是小分子抗肿瘤药物提供了灵感。
It is crucial to inhibit tumor growth and distant metastasis for breast cancer (BC) therapy. However, the treatment primarily dependent on surgery, chemotherapy, and radiotherapy is far from satisfactory. It had been demonstrated that the CXCL1/2-S100A8/9 axis played an essential role in BC therapy. Therefore, we constructed a natural product hydrogel for BC therapy by blocking CXCL1 signaling. The GK-GA (phytochemicals ofGenkwa Flos-glycyrrhizic acid) hydrogel was designed in a one-step “green” approach. The pharmacodynamics study showed GK-GA exhibited significant anti-tumor and anti-lung metastasis activities, resulting in the inhibition rate of tumor growth (IRG) over 90 % at 6.25 mg·kg−1, and did not display any obvious toxicity. In addition, the potent antitumor efficiency was also attributed to aggregation/assembly-induced retention (AIR) property. RNA sequencing analysis revealed the gene expression was significantly down-regulated in the GK-GA group, which were BCL2, CASP3, CXCL1, CXCL2, CXCR2, S100A8, S100A9, and confirmed further by western blot (WB). Our findings indicated natural product GK-GA hydrogel inhibited tumor growth and lung metastasis via the BCL2-CASP3 mitochondrial apoptosis pathway as well as the CXCL1/2-S100A8/9 pathway. This study provides inspiration for the fabrication of new excipients-free nano-dispersion in a one-step, no‐carrier‐added, organic solvent-free, “green” approach, particularly for small molecular antitumor agents.
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影响因子：
64.5
作者：
Acharyya S;Oskarsson T;Vanharanta S;Malladi S;Kim J;Morris PG;Manova-Todorova K;Leversha M;Hogg N;Seshan VE;Norton L;Brogi E;Massagué J
通讯作者：
Massagué J
影响因子：
6.1
作者：
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通讯作者：
Bin Wang;Heshan Xu;Xiaoying Hu;Wenyu Ma;Jian Zhang;Yuanfeng Li;Min Yu;Yaru Zhang;Xuegang Li;Xiaoli Ye
影响因子：
7.5
作者：
Li, Shizheng;Yuan, Song;Li, Kun
通讯作者：
Li, Kun
用于药物输送和癌症成像的肿瘤选择性级联可激活自滞系统
影响因子：
16.6
作者：
An, Hong-Wei;Li, Li-Li;Zhao, Yuliang
通讯作者：
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通过靶向和自组装信号增强光声探针进行趋化指导的细胞内金黄色葡萄球菌感染检测。
影响因子：
10.8
作者：
Cai, Qian;Fei, Yue;Wang, Hao
通讯作者：
Wang, Hao