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人参皂苷 Rg3 通过下调 C/EBPβ/NF-κB 信号通路抑制结直肠肿瘤生长。

Ginsenoside Rg3 inhibits colorectal tumor growth via down-regulation of C/EBPβ/NF-κB signaling.

机构信息

Department of Pharmacology, Medical School of Xi'an Jiaotong University, Xi'an, 710061, Shanxi, PR China; Department of Pharmacy, Gansu Provincial People's Hospital, Lanzhou, 730000, Gansu, PR China.

Department of Pharmacy, The People's Hospital of Pengzhou, Chengdu, 611900, Sichuan, PR China.

出版信息

Biomed Pharmacother. 2017 Dec;96:1240-1245. doi: 10.1016/j.biopha.2017.11.092. Epub 2017 Nov 21.

Abstract

Colorectal cancer (CRC), the third most frequent occurred cancer, is associated with high mortality and extremely poor prognosis. Ginsenoside Rg3 (Rg3), one of the pharmacologically active components of traditional Chinese herbal medicine Panax ginseng, exerts antitumor effects against several types of cancer growth, including colorectal cancer. However, the detailed molecular mechanisms and particularly the signaling pathways that are decisive in this process are not yet fully elucidated. The present study was carried out to determine the antitumor effects of Rg3 using human colorectal cells in vitro and Xenograft tumor model of human colon cancer in vivo. We found that Rg3 effectively suppressed the proliferation of cancer cells in three human colorectal cancer cell lines (HCT116, HT29, SW480). In addition, intraperitoneal injection of Rg3 for 3 weeks significantly inhibited the growth of xenografts in nude mice. Furthermore, we determined the potential underlying mechanisms for these actions. Treatment with Rg3 significantly inhibited the transactivation of C/EBPβ and NF-κB, as well as the association of C/EBPβ with p65-NFκB in nucleus. However, when SW-480 cells were co-transfected with C/EBPβ, or pretreatment with TNFα, Rg3 failed to inhibit tumor growth. Taken together, our results revealed a robust anti-tumor effect of Rg3, which is mediated by inhibition of C/EBPβ/NF-κB signaling.

摘要

结直肠癌(CRC)是第三大常见癌症,与高死亡率和极差的预后相关。人参皂苷 Rg3(Rg3)是传统中药人参的一种具有药理活性的成分,对多种类型的癌症生长具有抗肿瘤作用,包括结直肠癌。然而,其详细的分子机制,特别是在这个过程中起决定作用的信号通路尚未完全阐明。本研究旨在通过体外培养的人结直肠细胞和体内人结肠癌的异种移植肿瘤模型来确定 Rg3 的抗肿瘤作用。我们发现 Rg3 能有效抑制三种人结直肠癌细胞系(HCT116、HT29、SW480)中癌细胞的增殖。此外,Rg3 腹腔注射 3 周可显著抑制裸鼠异种移植瘤的生长。此外,我们还确定了这些作用的潜在机制。Rg3 处理显著抑制了 C/EBPβ和 NF-κB 的反式激活,以及 C/EBPβ与核内 p65-NFκB 的结合。然而,当 SW-480 细胞共转染 C/EBPβ或用 TNFα预处理时,Rg3 未能抑制肿瘤生长。总之,我们的结果揭示了 Rg3 的强大抗肿瘤作用,其机制是通过抑制 C/EBPβ/NF-κB 信号通路。

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