Di Jin, Chang-Qing Gui, Qian-Qian Ye, Guo-Fang Deng, Chang-Ling Zhu, Li Xu
{"title":"[人参皂苷- rg5协同伊马替尼通过PI3K/AKT/mTOR途径增强抗慢性髓系白血病K562细胞活性]。","authors":"Di Jin, Chang-Qing Gui, Qian-Qian Ye, Guo-Fang Deng, Chang-Ling Zhu, Li Xu","doi":"10.19746/j.cnki.issn.1009-2137.2025.01.001","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>To investigate the synergistic effect and its mechanism of ginsenoside-Rg5 in combination with imatinib in inhibiting proliferation of chronic myeloid leukemia K562 cells.</p><p><strong>Methods: </strong>K562 cells were treated with ginsenoside-Rg5 and imatinib. Cell survival was detected by CCK-8 assay, and IC<sub>50</sub> were calculated separately for each drug. Based on the value of IC<sub>50</sub> of ginsenoside-Rg5 and imatinib, an appropriate concentration gradient was selected for the combination. The synergistic effect of the two drug was analyzed using the online software synergy finder. The effects of single or combination therapy on apoptosis rate and the cell cycle distribution of K562 cells were analyzed by flow cytometry. Western blot was used to detect the expression of PI3K/AKT/mTOR signaling pathway related proteins and apoptosis related proteins in K562 cells after single or combination therapy.</p><p><strong>Results: </strong>Ginsenoside-Rg5 and imatinib were able to inhibit the proliferative activity of K562 cells in a dosedependent manner(<i>r</i> =-0.991， <i>r</i> =-0.942). The synergy score ZIP >10 was measured by Synergy Finder online software, indicating that ginsenoside-Rg5 and imatinib act synergistically on K562 cells. The apoptotic rates of K562 cells after single treatments with ginsenoside-Rg5 and imatinib were 11.96% and 8.13%, respectively, while the rate increased to 21.35% with the combination of two drugs, the apoptosis rate in the combination group was higher than that in the single-drug group ( <i>P</i> <0.05). The proportion of K562 cells in the G<sub>0</sub>/G<sub>1</sub> phase was significantly increased with the combined treatment of two drugs( <i>P</i> <0.05). The protein expression levels of p-PI3K, p-AKT, p-mTOR in K562 cells treated with the combination were significantly decreased, with noticeable downregulation of BCL-2 and upregulation of BAX, leading to a decreased Bcl-2/BAX ratio, while no significant changes were observed in the non-phosphorylated forms of PI3K, AKT, and mTOR proteins.</p><p><strong>Conclusion: </strong>The combination of ginsenoside-Rg5 and imatinib can inhibit the proliferation of CML cells and induce apoptosis, and the mechanism may act through PI3K/AKT/mTOR signaling pathways.</p>","PeriodicalId":35777,"journal":{"name":"中国实验血液学杂志","volume":"33 1","pages":"1-8"},"PeriodicalIF":0.0000,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"[Ginsenoside-Rg5 Synergizes with Imatinib to Enhances the Anti-Chronic Myeloid Leukemia K562 Cell Activity through PI3K/AKT/mTOR Pathway].\",\"authors\":\"Di Jin, Chang-Qing Gui, Qian-Qian Ye, Guo-Fang Deng, Chang-Ling Zhu, Li Xu\",\"doi\":\"10.19746/j.cnki.issn.1009-2137.2025.01.001\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>To investigate the synergistic effect and its mechanism of ginsenoside-Rg5 in combination with imatinib in inhibiting proliferation of chronic myeloid leukemia K562 cells.</p><p><strong>Methods: </strong>K562 cells were treated with ginsenoside-Rg5 and imatinib. Cell survival was detected by CCK-8 assay, and IC<sub>50</sub> were calculated separately for each drug. Based on the value of IC<sub>50</sub> of ginsenoside-Rg5 and imatinib, an appropriate concentration gradient was selected for the combination. The synergistic effect of the two drug was analyzed using the online software synergy finder. The effects of single or combination therapy on apoptosis rate and the cell cycle distribution of K562 cells were analyzed by flow cytometry. Western blot was used to detect the expression of PI3K/AKT/mTOR signaling pathway related proteins and apoptosis related proteins in K562 cells after single or combination therapy.</p><p><strong>Results: </strong>Ginsenoside-Rg5 and imatinib were able to inhibit the proliferative activity of K562 cells in a dosedependent manner(<i>r</i> =-0.991， <i>r</i> =-0.942). The synergy score ZIP >10 was measured by Synergy Finder online software, indicating that ginsenoside-Rg5 and imatinib act synergistically on K562 cells. The apoptotic rates of K562 cells after single treatments with ginsenoside-Rg5 and imatinib were 11.96% and 8.13%, respectively, while the rate increased to 21.35% with the combination of two drugs, the apoptosis rate in the combination group was higher than that in the single-drug group ( <i>P</i> <0.05). The proportion of K562 cells in the G<sub>0</sub>/G<sub>1</sub> phase was significantly increased with the combined treatment of two drugs( <i>P</i> <0.05). The protein expression levels of p-PI3K, p-AKT, p-mTOR in K562 cells treated with the combination were significantly decreased, with noticeable downregulation of BCL-2 and upregulation of BAX, leading to a decreased Bcl-2/BAX ratio, while no significant changes were observed in the non-phosphorylated forms of PI3K, AKT, and mTOR proteins.</p><p><strong>Conclusion: </strong>The combination of ginsenoside-Rg5 and imatinib can inhibit the proliferation of CML cells and induce apoptosis, and the mechanism may act through PI3K/AKT/mTOR signaling pathways.</p>\",\"PeriodicalId\":35777,\"journal\":{\"name\":\"中国实验血液学杂志\",\"volume\":\"33 1\",\"pages\":\"1-8\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2025-02-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"中国实验血液学杂志\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.19746/j.cnki.issn.1009-2137.2025.01.001\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"Medicine\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"中国实验血液学杂志","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.19746/j.cnki.issn.1009-2137.2025.01.001","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"Medicine","Score":null,"Total":0}
[Ginsenoside-Rg5 Synergizes with Imatinib to Enhances the Anti-Chronic Myeloid Leukemia K562 Cell Activity through PI3K/AKT/mTOR Pathway].
Objective: To investigate the synergistic effect and its mechanism of ginsenoside-Rg5 in combination with imatinib in inhibiting proliferation of chronic myeloid leukemia K562 cells.
Methods: K562 cells were treated with ginsenoside-Rg5 and imatinib. Cell survival was detected by CCK-8 assay, and IC50 were calculated separately for each drug. Based on the value of IC50 of ginsenoside-Rg5 and imatinib, an appropriate concentration gradient was selected for the combination. The synergistic effect of the two drug was analyzed using the online software synergy finder. The effects of single or combination therapy on apoptosis rate and the cell cycle distribution of K562 cells were analyzed by flow cytometry. Western blot was used to detect the expression of PI3K/AKT/mTOR signaling pathway related proteins and apoptosis related proteins in K562 cells after single or combination therapy.
Results: Ginsenoside-Rg5 and imatinib were able to inhibit the proliferative activity of K562 cells in a dosedependent manner(r =-0.991， r =-0.942). The synergy score ZIP >10 was measured by Synergy Finder online software, indicating that ginsenoside-Rg5 and imatinib act synergistically on K562 cells. The apoptotic rates of K562 cells after single treatments with ginsenoside-Rg5 and imatinib were 11.96% and 8.13%, respectively, while the rate increased to 21.35% with the combination of two drugs, the apoptosis rate in the combination group was higher than that in the single-drug group ( P <0.05). The proportion of K562 cells in the G0/G1 phase was significantly increased with the combined treatment of two drugs( P <0.05). The protein expression levels of p-PI3K, p-AKT, p-mTOR in K562 cells treated with the combination were significantly decreased, with noticeable downregulation of BCL-2 and upregulation of BAX, leading to a decreased Bcl-2/BAX ratio, while no significant changes were observed in the non-phosphorylated forms of PI3K, AKT, and mTOR proteins.
Conclusion: The combination of ginsenoside-Rg5 and imatinib can inhibit the proliferation of CML cells and induce apoptosis, and the mechanism may act through PI3K/AKT/mTOR signaling pathways.
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