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人参皂苷 Rk1 通过线粒体膜电位丧失和半胱天冬酶激活诱导神经母细胞瘤细胞凋亡。

Ginsenoside Rk1 Induces Apoptosis in Neuroblastoma Cells Through Loss of Mitochondrial Membrane Potential and Activation of Caspases.

机构信息

Department of Physiology, Chonbuk National University Medical School, Jeonju 54907, Korea.

Department of Anesthesiology and Pain Medicine, Chonbuk National University Hospital, Jeonju 54907, Korea.

出版信息

Int J Mol Sci. 2019 Mar 11;20(5):1213. doi: 10.3390/ijms20051213.

DOI:10.3390/ijms20051213
PMID:30862004
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6429382/
Abstract

Neuroblastoma (NB) is the most common childhood cancer, with a very poor prognosis. More than 60% of children with NB die within five years; therefore, a more effective therapy for NB is required. Although ginsenoside has been shown to significantly inhibit the growth of various cancers, the effect of ginsenoside Rk1 on neuroblastoma has not been known yet. Hence, we examined the anticancer effects of highly pure Rk1 on neuroblastoma cell lines. The apoptotic effects of Rk1 on neuroblastoma cells were examined using cell viability assay, flow cytometry and cell staining assay, and the change in gene expression levels were analysed using RT-PCR, western blots, and immunohistochemistry. The metastatic effect of Rk1 was monitored by wound healing assay, invasion and migration with Matrigels. Rk1 inhibited neuroblastoma cell viability dose-dependently. Rk1-induced apoptosis was investigated through nuclear condensation and mitochondrial membrane potential loss, and it showed that Rk1 can induce cell cycle arrest at the G0/G1 phase but also inhibit the metastatic ability of neuroblastoma cells. Moreover, Rk1 (30 mg/kg) injections markedly inhibited xenograft tumor growth. These findings demonstrate that Rk1 might be valuable in the development of anti-cancer agents for neuroblastoma treatment.

摘要

神经母细胞瘤(NB)是儿童中最常见的癌症,预后极差。超过 60%的 NB 患儿在五年内死亡;因此,需要更有效的 NB 治疗方法。虽然已表明人参皂苷能显著抑制多种癌症的生长,但尚未了解人参皂苷 Rk1 对神经母细胞瘤的影响。因此,我们研究了高纯度 Rk1 对神经母细胞瘤细胞系的抗癌作用。使用细胞活力测定、流式细胞术和细胞染色测定检查 Rk1 对神经母细胞瘤细胞的凋亡作用,并使用 RT-PCR、western blot 和免疫组织化学分析基因表达水平的变化。通过划痕愈合测定、Matrigel 中的侵袭和迁移监测 Rk1 的转移效应。Rk1 呈剂量依赖性抑制神经母细胞瘤细胞活力。通过核浓缩和线粒体膜电位丧失研究了 Rk1 诱导的细胞凋亡,结果表明 Rk1 可以诱导细胞周期停滞在 G0/G1 期,但也抑制神经母细胞瘤细胞的转移能力。此外,Rk1(30mg/kg)注射显著抑制异种移植肿瘤生长。这些发现表明 Rk1 可能对开发用于神经母细胞瘤治疗的抗癌药物具有重要价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/776d/6429382/1c7548fddafc/ijms-20-01213-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/776d/6429382/8a15522a6a60/ijms-20-01213-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/776d/6429382/2b7f29bb2241/ijms-20-01213-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/776d/6429382/83c9628e4849/ijms-20-01213-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/776d/6429382/9a600c5dba16/ijms-20-01213-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/776d/6429382/824c99a088b7/ijms-20-01213-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/776d/6429382/1c7548fddafc/ijms-20-01213-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/776d/6429382/8a15522a6a60/ijms-20-01213-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/776d/6429382/2b7f29bb2241/ijms-20-01213-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/776d/6429382/83c9628e4849/ijms-20-01213-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/776d/6429382/9a600c5dba16/ijms-20-01213-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/776d/6429382/824c99a088b7/ijms-20-01213-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/776d/6429382/1c7548fddafc/ijms-20-01213-g006.jpg

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