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清热消积方调控 GC 中 M2 TAM 的 miR-29 分化。

Qingrexiaoji Recipe Regulates the Differentiation of M2 TAM miR-29 in GC.

机构信息

Department of First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.

Department of Integrated Chinese and Western Medicine, The First People's Hospital of Wenling, Taizhou, Zhejiang, China.

出版信息

Comb Chem High Throughput Screen. 2024;27(18):2764-2775. doi: 10.2174/0113862073263776231009115524.

Abstract

BACKGROUND

Gastric cancer, one of the most familiar adenocarcinomas of the gastrointestinal tract, ranks third in the world in cancer-related deaths. Traditional Chinese medicine can suppress the growth of tumors, and the underlying mechanism may be associated with the tumor microenvironment. Here, we investigated the anti-cancer effects of the Qingrexiaoji recipe on gastric cancer and the underlying molecular mechanism.

METHODS

An nude mouse model was established, and the expression of CD206, CD80, and M2 phenotype-related proteins (Arg-1, Fizz1) was obtained by flow cytometry and western blotting. The expressions of the M2 phenotype-related cytokines were examined by ELISA.

RESULTS

inhibited gastric tumor growth and downregulated the expression of CD206, IFN-γ, IL-13, IL-4, and TNF-α deceased M2 phenotypic polarization by upregulating microRNA (miR)-29a-3p level. Luciferase activity assays showed that HDAC4 is a potential target of miR-29a-3p. In cells co-transfected with HDAC4 siRNA and miR-29a-3p inhibitor and treated with IL-4 and , the miR-29a-3p inhibitorinduced increase of M2 phenotypic polarization was reversed.

CONCLUSION

In summary, these results suggested that the Qingrexiaoji recipe regulated M2 macrophage polarization by regulating miR-29a-3p/HDAC4, providing a different and innovative treatment for gastric cancer.

摘要

背景

胃癌是最常见的胃肠道腺癌之一,在癌症相关死亡中位居世界第三。中药可以抑制肿瘤生长,其潜在机制可能与肿瘤微环境有关。在这里,我们研究了清热消积方对胃癌的抗癌作用及其潜在的分子机制。

方法

建立裸鼠模型,通过流式细胞术和蛋白质印迹法检测 CD206、CD80 和 M2 表型相关蛋白(Arg-1、Fizz1)的表达。通过 ELISA 检测 M2 表型相关细胞因子的表达。

结果

清热消积方抑制胃肿瘤生长,并下调 CD206、IFN-γ、IL-13、IL-4 和 TNF-α 的表达,通过上调 microRNA(miR)-29a-3p 水平抑制 M2 表型极化。荧光素酶活性测定表明,HDAC4 是 miR-29a-3p 的潜在靶标。在共转染 HDAC4 siRNA 和 miR-29a-3p 抑制剂并经 IL-4 和 处理的细胞中,miR-29a-3p 抑制剂诱导的 M2 表型极化增加被逆转。

结论

综上所述,这些结果表明,清热消积方通过调节 miR-29a-3p/HDAC4 来调节 M2 巨噬细胞极化,为胃癌提供了一种不同的创新治疗方法。

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