Shu-Guang Du, Hua-Min Zhang, Yun-Xia Ji, Yu-Lin Tian, Dan Wang, Kun Zhu, Qing-Gao Zhang, Shuang-Ping Liu
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引用次数: 0
摘要
多粘菌素 VII 是一种从传统中药重楼中提取的具有生物活性的中药单体。许多研究表明,多粘菌素 VII 对结肠癌、肝癌和肺癌等多种癌症具有抗癌活性,但其对乳腺癌的作用尚未阐明。在这项研究中,我们证明多花植物蛋白 VII 可抑制乳腺癌细胞的增殖、增加细胞内活性氧的产生以及降低线粒体膜电位。值得注意的是,多粘菌素 VII 还能通过线粒体途径诱导细胞凋亡。研究人员利用转录组测序分析了 PPVII 在调控乳腺癌细胞方面的靶标。机理研究表明,PPVII 能下调 Son of Sevenless1(SOS1),抑制 MAPK/ERK 通路。此外,PPVII 在体内对注射了乳腺癌细胞的裸鼠产生了很强的抗肿瘤作用。我们的研究结果表明,PPVII 可通过调节 SOS1/MAPK/ERK 通路促进细胞凋亡,因此可能成为治疗乳腺癌的候选靶点。
Polyphyllin VII Promotes Apoptosis in Breast Cancer by Inhibiting MAPK/ERK Signaling Pathway through Downregulation of SOS1.
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 vivo 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.