Red ginseng polysaccharide promotes ferroptosis in gastric cancer cells by inhibiting PI3K/Akt pathway through down-regulation of AQP3.

IF 4.4 4区医学 Q2 ONCOLOGY Cancer Biology & Therapy Pub Date : 2024-12-31 Epub Date: 2023-12-05 DOI:10.1080/15384047.2023.2284849

Yan Wang, Wen-Xian Guan, Yuan Zhou, Xiao-Yu Zhang, Hai-Jian Zhao

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Abstract

Objective: This study aims to investigate the effect of red ginseng polysaccharide (RGP) on gastric cancer (GC) development and explore its mechanism.

Methods: GC cell lines AGS were treated with varying concentrations of RGP (50, 100, and 200 μg/mL). AGS cells treated with 200 μg/mL RGP were transfected with aquaporin 3 (AQP3) overexpression vector. Cell proliferation, viability, and apoptosis were evaluated by MTT, colony formation assay, and flow cytometry, respectively. Real-time quantitative reverse transcription PCR (qRT-PCR) was used to detect the expression of AQP3. The levels of Fe2+, malondialdehyde, and lactate dehydrogenase were measured using their respective detection kits, and the reactive oxygen species levels was determined by probe 2',7'-dichlorodihydrofluorescein diacetate. The expression of ferroptosis-related protein and PI3K/Akt pathway-related protein were assessed by western blot. In vivo experiments in nude mice were performed and the mice were divided into four groups (n = 5/group) which gavage administrated with 150 mg/kg normal saline, and 75, 150, 300 mg/kg RGP, respectively. Their tumor weight and volume were recorded.

Results: RGP treatment effectively inhibited the proliferation and viability of AGS cells in a dosage-dependent manner and induced apoptosis. It induced ferroptosis in AGS cells, as well as inhibiting the expression of PI3K/Akt-related proteins. AQP3 overexpression could reversed the effect of RGP treatment on ferroptosis. Confirmatory in vivo experiments showed that RGP could reduce the growth of implanted tumor, with increased RGP concentration resulting in greater tumor inhibitory effects.

Conclusion: RGP might have therapeutic potential against GC, effectively inhibiting the proliferation and viability of AGS cells.

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红参多糖通过下调 AQP3 抑制 PI3K/Akt 通路，促进胃癌细胞的铁变态反应。

研究目的本研究旨在探讨红参多糖（RGP）对胃癌（GC）发展的影响及其机制：方法：用不同浓度的 RGP（50、100 和 200 μg/mL）处理胃癌细胞株 AGS。用 200 μg/mL RGP 处理的 AGS 细胞转染水蒸蛋白 3（AQP3）过表达载体。细胞增殖、活力和凋亡分别通过 MTT、集落形成试验和流式细胞术进行评估。实时定量反转录 PCR（qRT-PCR）用于检测 AQP3 的表达。Fe2+、丙二醛和乳酸脱氢酶的水平用各自的检测试剂盒进行检测，活性氧水平用探针 2',7'-二氯二氢荧光素二乙酸酯进行检测。铁突变相关蛋白和 PI3K/Akt 通路相关蛋白的表达采用 Western 印迹法进行评估。裸鼠体内实验将小鼠分为四组（n = 5/组），分别灌胃 150 毫克/千克生理盐水和 75、150、300 毫克/千克 RGP。记录肿瘤重量和体积：结果：RGP 能有效抑制 AGS 细胞的增殖和存活，并诱导细胞凋亡，其抑制作用与剂量有关。它还能诱导 AGS 细胞的铁凋亡，并抑制 PI3K/Akt 相关蛋白的表达。AQP3 的过表达可以逆转 RGP 对铁细胞凋亡的影响。体内实验证实，RGP可减少植入肿瘤的生长，增加RGP浓度可产生更大的肿瘤抑制作用：结论：RGP 可有效抑制 AGS 细胞的增殖和活力，具有治疗 GC 的潜力。

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来源期刊

Cancer Biology & Therapy 医学-肿瘤学

CiteScore

7.00

自引率

0.00%

发文量

审稿时长

2.3 months

期刊介绍： Cancer, the second leading cause of death, is a heterogenous group of over 100 diseases. Cancer is characterized by disordered and deregulated cellular and stromal proliferation accompanied by reduced cell death with the ability to survive under stresses of nutrient and growth factor deprivation, hypoxia, and loss of cell-to-cell contacts. At the molecular level, cancer is a genetic disease that develops due to the accumulation of mutations over time in somatic cells. The phenotype includes genomic instability and chromosomal aneuploidy that allows for acceleration of genetic change. Malignant transformation and tumor progression of any cell requires immortalization, loss of checkpoint control, deregulation of growth, and survival. A tremendous amount has been learned about the numerous cellular and molecular genetic changes and the host-tumor interactions that accompany tumor development and progression. It is the goal of the field of Molecular Oncology to use this knowledge to understand cancer pathogenesis and drug action, as well as to develop more effective diagnostic and therapeutic strategies for cancer. This includes preventative strategies as well as approaches to treat metastases. With the availability of the human genome sequence and genomic and proteomic approaches, a wealth of tools and resources are generating even more information. The challenge will be to make biological sense out of the information, to develop appropriate models and hypotheses and to translate information for the clinicians and the benefit of their patients. Cancer Biology & Therapy aims to publish original research on the molecular basis of cancer, including articles with translational relevance to diagnosis or therapy. We will include timely reviews covering the broad scope of the journal. The journal will also publish op-ed pieces and meeting reports of interest. The goal is to foster communication and rapid exchange of information through timely publication of important results using traditional as well as electronic formats. The journal and the outstanding Editorial Board will strive to maintain the highest standards for excellence in all activities to generate a valuable resource.