School of Functional Food and Wine, Shenyang Pharmaceutical University, Shenyang 110016, China.
School of Functional Food and Wine, Shenyang Pharmaceutical University, Shenyang 110016, China.
Bioorg Chem. 2022 Sep;126:105913. doi: 10.1016/j.bioorg.2022.105913. Epub 2022 May 26.
Due to its aggressiveness and high metastasis rates, triple-negative breast cancer (TNBC) is a ubiquitous and deadly disease for the majority of women globally. Gypensapogenin H (GH) is a novel dammarane-type triterpene isolated from hydrolyzate of total saponins from Gynostemma pentaphyllum. Our previous work demonstrated that GH promoted apoptosis in TNBC. In the present study, xenograft TNBC models (xenotransplantation of MDA-MB-231 cells in nude mice) were used to evaluate the efficacy of GH in vivo. We preliminarily predicted the mechanism of GH inhibiting breast cancer tumors at the gene level through transcriptome screening. Through western blot analysis of tumor tissue, we found that GH could inhibit tumor proliferation and migration by regulating the PI3K/AKT/NF-κB/MMP-9 signaling pathway in vivo. We also analyzedthe results at the cell level in vitro, which were consistent with those in vivo. In summary, GH inhibited TNBC growth in vivo and suppressed TNBC cell migration in vitro. Our findings could help understand the mechanism of action of GH and suggest that GH would be a promising agent for TNBC therapy.
由于其侵袭性和高转移率，三阴性乳腺癌（TNBC）是全球大多数女性普遍存在且致命的疾病。琴叶榕皂苷元 H（GH）是一种从绞股蓝总皂苷水解产物中分离得到的新型达玛烷型三萜。我们之前的工作表明，GH 能促进 TNBC 细胞凋亡。在本研究中，我们使用异种移植 TNBC 模型（裸鼠 MDA-MB-231 细胞移植）在体内评估 GH 的疗效。我们通过转录组筛选初步预测了 GH 抑制乳腺癌肿瘤的基因水平的机制。通过肿瘤组织的 Western blot 分析，我们发现 GH 可以通过调节 PI3K/AKT/NF-κB/MMP-9 信号通路在体内抑制肿瘤增殖和迁移。我们还在体外的细胞水平上分析了这些结果，与体内的结果一致。总之，GH 抑制了体内 TNBC 的生长，并抑制了体外 TNBC 细胞的迁移。我们的研究结果有助于了解 GH 的作用机制，并表明 GH 可能成为 TNBC 治疗的一种有前途的药物。
