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

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 transfect...

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Main Authors: Yan Wang, Wen-Xian Guan, Yuan Zhou, Xiao-Yu Zhang, Hai-Jian Zhao
Format: Article
Language:English
Published: Taylor & Francis Group 2024-12-01
Series:Cancer Biology & Therapy
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Online Access:https://www.tandfonline.com/doi/10.1080/15384047.2023.2284849
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author Yan Wang
Wen-Xian Guan
Yuan Zhou
Xiao-Yu Zhang
Hai-Jian Zhao
author_facet Yan Wang
Wen-Xian Guan
Yuan Zhou
Xiao-Yu Zhang
Hai-Jian Zhao
author_sort Yan Wang
collection DOAJ
description 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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institution Kabale University
issn 1538-4047
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publishDate 2024-12-01
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series Cancer Biology & Therapy
spelling doaj-art-1be652e1430340d6bbb39c37645e73852024-12-13T06:53:24ZengTaylor & Francis GroupCancer Biology & Therapy1538-40471555-85762024-12-0125110.1080/15384047.2023.2284849Red ginseng polysaccharide promotes ferroptosis in gastric cancer cells by inhibiting PI3K/Akt pathway through down-regulation of AQP3Yan Wang0Wen-Xian Guan1Yuan Zhou2Xiao-Yu Zhang3Hai-Jian Zhao4Department of General Surgery, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, ChinaDepartment of General Surgery, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, ChinaDepartment of Gastrointestinal Surgery, The Affiliated Huai’an Hospital of Xuzhou Medical University, Huai’an, ChinaDepartment of Gastrointestinal Surgery, The Affiliated Huai’an Hospital of Xuzhou Medical University, Huai’an, ChinaDepartment of Gastrointestinal Surgery, The Affiliated Huai’an Hospital of Xuzhou Medical University, Huai’an, ChinaObjective 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.https://www.tandfonline.com/doi/10.1080/15384047.2023.2284849Gastric cancerred ginseng polysaccharideaquaporin 3ferroptosisPI3K/Akt pathway
spellingShingle Yan Wang
Wen-Xian Guan
Yuan Zhou
Xiao-Yu Zhang
Hai-Jian Zhao
Red ginseng polysaccharide promotes ferroptosis in gastric cancer cells by inhibiting PI3K/Akt pathway through down-regulation of AQP3
Cancer Biology & Therapy
Gastric cancer
red ginseng polysaccharide
aquaporin 3
ferroptosis
PI3K/Akt pathway
title Red ginseng polysaccharide promotes ferroptosis in gastric cancer cells by inhibiting PI3K/Akt pathway through down-regulation of AQP3
title_full Red ginseng polysaccharide promotes ferroptosis in gastric cancer cells by inhibiting PI3K/Akt pathway through down-regulation of AQP3
title_fullStr Red ginseng polysaccharide promotes ferroptosis in gastric cancer cells by inhibiting PI3K/Akt pathway through down-regulation of AQP3
title_full_unstemmed Red ginseng polysaccharide promotes ferroptosis in gastric cancer cells by inhibiting PI3K/Akt pathway through down-regulation of AQP3
title_short Red ginseng polysaccharide promotes ferroptosis in gastric cancer cells by inhibiting PI3K/Akt pathway through down-regulation of AQP3
title_sort red ginseng polysaccharide promotes ferroptosis in gastric cancer cells by inhibiting pi3k akt pathway through down regulation of aqp3
topic Gastric cancer
red ginseng polysaccharide
aquaporin 3
ferroptosis
PI3K/Akt pathway
url https://www.tandfonline.com/doi/10.1080/15384047.2023.2284849
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