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巴卡丁通过抑制肝癌中的 M2 表型巨噬细胞抑制细胞增殖和转移并增强卡瑞利珠单抗的抗肿瘤作用。

Babaodan inhibits cell proliferation and metastasis and enhances anti-tumor effects of camrelizumab by inhibiting M2 phenotype macrophages in hepatocellular carcinoma.

机构信息

State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.

School of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.

出版信息

J Ethnopharmacol. 2024 Nov 15;334:118540. doi: 10.1016/j.jep.2024.118540. Epub 2024 Jul 9.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Babaodan (BBD) is a unique Chinese medication utilized in traditional Chinese medicine. It can eliminate toxins, induce diuresis, and eliminate yellowish hue. In addition to treating acute and chronic viral hepatitis, cholecystitis, cholangitis, and urinary tract infections, BBD has garnered popularity as a substitution treatment for several malignant cancers, particularly hepatocellular carcinoma (HCC).

AIM OF THE STUDY

To elucidate the efficacy and mechanism of BBD alone and combined with camrelizumab (CLM) for treating HCC.

METHODS

We investigated the effects of BBD on the HCC tumor microenvironment in vivo. Furthermore, we evaluated its effects on tumor growth and metastasis induced by M2 macrophages in vitro.

RESULTS

In a mouse model of orthotopic HCC, BBD decreased tumor growth. Furthermore, it increased the M1/M2 macrophage ratio and CD8 T-cell abundance in mice. In addition, BBD reversed HCC cell proliferation and metastasis induced by M2 macrophages, increased the anti-HCC effect of low-dose CLM, and attenuated organ damage induced by high-dose CLM. Lastly, BBD enhanced the efficacy of CLM via the PI3K/AKT/mTOR signaling pathway.

CONCLUSION

BBD increases the antitumor effect of CLM by modulating the tumor immune microenvironment and attenuating its the toxic side effects of CLM.

摘要

民族药理学相关性

八宝鸡(BBD)是一种独特的中药,用于中医。它可以排毒、利尿、去黄。除了治疗急性和慢性病毒性肝炎、胆囊炎、胆管炎和尿路感染外,BBD 还因其作为几种恶性癌症的替代治疗而受到欢迎,特别是肝细胞癌(HCC)。

研究目的

阐明 BBD 单独和联合卡瑞利珠单抗(CLM)治疗 HCC 的疗效和机制。

方法

我们研究了 BBD 对体内 HCC 肿瘤微环境的影响。此外,我们评估了它对 M2 巨噬细胞诱导的肿瘤生长和转移的影响。

结果

在原位 HCC 小鼠模型中,BBD 可降低肿瘤生长。此外,它增加了小鼠中 M1/M2 巨噬细胞的比例和 CD8 T 细胞的丰度。此外,BBD 逆转了 M2 巨噬细胞诱导的 HCC 细胞增殖和转移,增加了低剂量 CLM 的抗 HCC 作用,并减轻了高剂量 CLM 引起的器官损伤。最后,BBD 通过 PI3K/AKT/mTOR 信号通路增强了 CLM 的疗效。

结论

BBD 通过调节肿瘤免疫微环境并减轻 CLM 的毒副作用来增强 CLM 的抗肿瘤作用。

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