人参皂苷 Rk1 诱导 MDA-MB-231 三阴性乳腺癌细胞周期停滞和凋亡。

Ginsenoside Rk1 induces cell cycle arrest and apoptosis in MDA-MB-231 triple negative breast cancer cells.

机构信息

Shaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering, Northwest University, 229 Taibai North Road, Xi'an, Shaanxi, 710069, China; Shaanxi R&D Center of Biomaterials and Fermentation Engineering, School of Chemical Engineering, Northwest University, 229 Taibai North Road, Xi'an, Shaanxi, 710069, China; Biotech. & Biomed. Research Institute, Northwest University, 229 Taibai North Road, Xi'an, Shaanxi 710069, China.

出版信息

Toxicology. 2019 Apr 15;418:22-31. doi: 10.1016/j.tox.2019.02.010. Epub 2019 Feb 21.

DOI:10.1016/j.tox.2019.02.010

PMID:30797898

Abstract

Ginsenoside Rk1 (Rk1) is a component found in processed ginseng that exhibits anti-insulin resistance, anti-inflammation and anti-cancer activities. However, there are few reports of Rk1 activity against triple negative breast cancer (TNBC). In this study, the anti-proliferation and potential mechanisms of Rk1 in MDA-MB-231 cells were investigated. Xenograft model exhibited that Rk1 significantly repressed tumor growth with low toxicity to major organs. Moreover, Rk1 dramatically inhibited cell proliferation, colony formation, promoted LDH release, and induced G/G phase arrest. Rk1 also triggered intracellular reactive oxygen species (ROS) generation and mitochondrial membrane potential reduction. Western blot results revealed that Rk1 increased the expression of Bax, cytochrome C, cleaved caspase 3, 8 and 9 levels and decreased Bcl-2 level and blocked the PI3K/Akt pathway. Pretreatment with the pan-caspase inhibitor Z-VAD-FMK, PI3K/Akt pathway activator insulin or ROS scavenger N-acetylcysteine (NAC) further demonstrated that ROS/PI3K/Akt pathway was responsible for Rk1-induced apoptosis. Overall, this is the first study to illustrate the anti-triple negative breast cancer effects and mechanisms of Rk1 and ginsenoside Rk1 could be a new promising anti-tumor drug for TNBC.

摘要

人参皂苷 Rk1（Rk1）是一种在加工人参中发现的成分，具有抗胰岛素抵抗、抗炎和抗癌活性。然而，关于 Rk1 对三阴性乳腺癌（TNBC）的活性的报道很少。在这项研究中，研究了 Rk1 在 MDA-MB-231 细胞中的抗增殖作用及其潜在机制。异种移植模型表明，Rk1 能显著抑制肿瘤生长，且对主要器官的毒性较低。此外，Rk1 能显著抑制细胞增殖、集落形成，促进 LDH 释放，并诱导 G1/G0 期阻滞。Rk1 还引发细胞内活性氧（ROS）的产生和线粒体膜电位的降低。Western blot 结果表明，Rk1 增加了 Bax、细胞色素 C、cleaved caspase 3、8 和 9 的表达水平，降低了 Bcl-2 水平，并阻断了 PI3K/Akt 通路。用泛半胱天冬酶抑制剂 Z-VAD-FMK、PI3K/Akt 通路激活剂胰岛素或 ROS 清除剂 N-乙酰半胱氨酸（NAC）预处理进一步表明，ROS/PI3K/Akt 通路是 Rk1 诱导细胞凋亡的原因。总的来说，这是首次阐明 Rk1 对三阴性乳腺癌的作用及其机制的研究，人参皂苷 Rk1 可能成为 TNBC 的一种有前途的新型抗肿瘤药物。