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人参皂苷 RG1 增强多柔比星诱导的 MDA-MB-231 乳腺癌细胞系的凋亡细胞死亡。

Ginsenoside RG1 augments doxorubicin-induced apoptotic cell death in MDA-MB-231 breast cancer cell lines.

机构信息

Department of Galactophore, Linyi Central Hospital, Linyi, China.

Thyroid and Breast Surgery Department, Chengdu Fifth People's Hospital, Sichuan Chengdu, China.

出版信息

J Biochem Mol Toxicol. 2022 Jan;36(1):e22945. doi: 10.1002/jbt.22945. Epub 2021 Nov 16.

DOI:10.1002/jbt.22945
PMID:34783124
Abstract

This study determined the chemosensitizing potential of ginsenoside Rg1 in triple-negative MDA-MB-231 breast cancer cell lines. Ginsenoside Rg1 (10 µM) treated breast cancer cells were exposed to 8 nM of doxorubicin, and the chemosensitizing potential was measured by cell-based assays. Ginsenoside Rg1 (10 µM) treatment lowered the doxorubicin IC value to 0.01 nM. Furthermore, the ginsenoside pretreatment augments doxorubicin-mediated reactive oxygen species (ROS) generation and subsequent alterations of mitochondrial membrane potential in MDA-MB-231 cell lines. The alkaline comet assay results illustrated an increased % tail DNA during ginsenoside Rg1 plus doxorubicin treatment than doxorubicin alone treatment. In addition, the number of apoptotic cells was also increased in ginsenoside Rg1 plus doxorubicin-treated cells. Furthermore, the polymerase chain reaction array results illustrate activation of mitogen-activated protein kinase (MAPK) gene expression (AKT, ERK, and MAPK) during doxorubicin alone treatment and it has been attenuated by ginsenoside Rg1 pretreatment. Moreover, ginsenoside Rg1 treatment before doxorubicin activates the DNA damage response elements (ATM, H2AX, RAD51, and XRCC1) and subsequent apoptosis-related gene expression (p21, TP53. APAF1, Bax, CASP3, and CASP9) patterns in MDA-MB-231 cell lines. The ginsenoside Rg1 plus doxorubicin combination shows less cytotoxicity and ROS generation in MDA10A normal breast cancer cell lines. Therefore, the present results support the chemosensitizing property of ginsenoside Rg1 in triple-negative breast cancer cell lines.

摘要

这项研究旨在确定人参皂苷 Rg1 对三阴性 MDA-MB-231 乳腺癌细胞系的化疗增敏作用。将浓度为 10µM 的人参皂苷 Rg1 处理后的乳腺癌细胞暴露于 8nM 的阿霉素中,并通过细胞检测来评估其化疗增敏作用。结果显示,人参皂苷 Rg1(10µM)处理可将阿霉素的 IC 值降低至 0.01nM。此外,人参皂苷预处理可增强 MDA-MB-231 细胞系中阿霉素介导的活性氧(ROS)生成及随后的线粒体膜电位改变。彗星试验结果表明,人参皂苷 Rg1 联合阿霉素处理时的 DNA 尾部百分比高于单独使用阿霉素处理时。此外,人参皂苷 Rg1 联合阿霉素处理组的凋亡细胞数量也有所增加。此外,聚合酶链反应基因芯片结果表明,阿霉素单独处理时可激活丝裂原活化蛋白激酶(MAPK)基因表达(AKT、ERK 和 MAPK),而人参皂苷 Rg1 预处理可减弱其作用。此外,在阿霉素处理之前用人参皂苷 Rg1 处理可激活 MDA-MB-231 细胞系中的 DNA 损伤反应元件(ATM、H2AX、RAD51 和 XRCC1)及随后的凋亡相关基因表达(p21、TP53、APAF1、Bax、CASP3 和 CASP9)模式。人参皂苷 Rg1 联合阿霉素在 MDA10A 正常乳腺癌细胞系中的细胞毒性和 ROS 生成较少。因此,这些结果支持人参皂苷 Rg1 对三阴性乳腺癌细胞系的化疗增敏作用。

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