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重楼皂苷VII通过下调SOS1抑制MAPK/ERK信号通路促进乳腺癌细胞凋亡。

Polyphyllin VII Promotes Apoptosis in Breast Cancer by Inhibiting MAPK/ERK Signaling Pathway through Downregulation of SOS1.

作者信息

Du Shu-Guang, Zhang Hua-Min, Ji Yun-Xia, Tian Yu-Lin, Wang Dan, Zhu Kun, Zhang Qing-Gao, Liu Shuang-Ping

机构信息

Chronic Disease Research Center, Medical College, Dalian University, Xuefu Road 10, Dalian 116622, P. R. China.

Laboratory Department, The First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin 150040, P. R. China.

出版信息

Am J Chin Med. 2024;52(3):885-904. doi: 10.1142/S0192415X24500368. Epub 2024 May 8.

Abstract

Polyphyllin VII is a biologically active herbal monomer extracted from the traditional Chinese herbal medicine Chonglou. Many studies have demonstrated the anticancer activity of polyphyllin VII against various types of cancers, such as colon, liver, and lung cancer, but its effect on breast cancer has not been elucidated. In this study, we demonstrate that polyphyllin VII inhibited proliferation, increased production of intracellular reactive oxygen species, and decreased mitochondrial membrane potential in breast cancer cells. Notably, polyphyllin VII also induced apoptosis via the mitochondrial pathway. Transcriptome sequencing was used to analyze the targets of PPVII in regulating breast cancer cells. Mechanistic studies showed that polyphyllin VII downregulated Son of Sevenless1 (SOS1) and inhibited the MAPK/ERK pathway. Furthermore, PPVII exerted strong antitumor effects in nude mice injected with breast cancer cells. Our results suggest that PPVII may promote apoptosis through regulating the SOS1/MAPK/ERK pathway, making it a possible candidate target for the treatment of breast cancer.

摘要

重楼皂苷VII是从传统中药重楼中提取的一种具有生物活性的草药单体。许多研究已经证明重楼皂苷VII对多种类型的癌症具有抗癌活性,如结肠癌、肝癌和肺癌,但其对乳腺癌的影响尚未阐明。在本研究中,我们证明重楼皂苷VII抑制乳腺癌细胞增殖,增加细胞内活性氧的产生,并降低线粒体膜电位。值得注意的是,重楼皂苷VII还通过线粒体途径诱导细胞凋亡。利用转录组测序分析了PPVII在调控乳腺癌细胞中的靶点。机制研究表明,重楼皂苷VII下调七号无翅型蛋白1(SOS1)并抑制MAPK/ERK通路。此外,PPVII对注射了乳腺癌细胞的裸鼠具有很强的抗肿瘤作用。我们的结果表明,PPVII可能通过调节SOS1/MAPK/ERK通路促进细胞凋亡,使其成为治疗乳腺癌的一个可能的候选靶点。

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