{"title":"基于网络药理学的Hederagenin联合L-OHP对AGS/L-OHP化疗敏感性影响的分子机制分析","authors":"Hongyue Tang, Chao Wang, Chenhao Xing, Guoxin Liang, Chang Guo, Xin Liu, YanJie Li, Mingming Zhang","doi":"10.2174/0115734099270389240104050955","DOIUrl":null,"url":null,"abstract":"<p><strong>Aims and objectives: </strong>This study aimed to evaluate the pharmacological mechanism of Hederagenin (HD) combined with oxaliplatin (L-OHP) in treating gastric cancer (GC) through network pharmacology combined with experimental verification.</p><p><strong>Material and methods: </strong>Network pharmacology methods were used to screen potential targets for HD, L-OHP, and GC-related targets from public databases, and the intersection of the three gene sets was taken. Cross genes were analyzed through protein-protein interaction (PPI) networks to predict core targets, and related pathways were predicted through GO and KEGG enrichment analysis. The experimental results were verified by the in vitro experiments. HD was applied on AGS/L-OHP cells, and then cellular chemosensitivity and the expressions of P-gp, Survivin, Bcl-2, p-Akt, and p-PI3K genes were detected. Wound assay and Transwell Chamber assay were employed to detect the effect of HD on AGS/L-OHP cells. Nude mice xenograft models transfected using AGS/L-OHP cells were also treated with HD in order to verify the results. The size and weight of the tumor, as well as the expressions of P-gp, Survivin, Bcl-2, p- Akt and p-PI3K genes, were also measured.</p><p><strong>Results: </strong>KEGG analysis showed that the anti-gastric cancer effect of HD was mediated mainly by PI3K-Akt signaling pathways. The PI3K-Akt signaling pathway containing more enriched genes may play a greater role in anti-gastric cancer. It was observed that for AGS/L-OHP cells jointly treated with HD and L-OHP, their activity, migration and invasion were significantly lower than those treated only using HD or L-OHP group. Moreover, expressions of p-Akt, p- PI3K, Bcl-2, P-gp, and Survivin for the HD+L-OHP group decreased significantly. Results of the in vivo experiments showed that the sizes and weights of tumors in the HD+L-OHP group were the lowest compared to the HD group and L-OHP group.</p><p><strong>Conclusion: </strong>Our findings suggest that HD may reduce the resistance of AGS/L-OHP cells to LOHP by regulating the PI3K/Akt signaling pathway.</p>","PeriodicalId":93961,"journal":{"name":"Current computer-aided drug design","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Molecular Mechanism Analysis of the Effect of Hederagenin Combined with L-OHP on Chemosensitivity of AGS/L-OHP Based on Network Pharmacology.\",\"authors\":\"Hongyue Tang, Chao Wang, Chenhao Xing, Guoxin Liang, Chang Guo, Xin Liu, YanJie Li, Mingming Zhang\",\"doi\":\"10.2174/0115734099270389240104050955\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Aims and objectives: </strong>This study aimed to evaluate the pharmacological mechanism of Hederagenin (HD) combined with oxaliplatin (L-OHP) in treating gastric cancer (GC) through network pharmacology combined with experimental verification.</p><p><strong>Material and methods: </strong>Network pharmacology methods were used to screen potential targets for HD, L-OHP, and GC-related targets from public databases, and the intersection of the three gene sets was taken. Cross genes were analyzed through protein-protein interaction (PPI) networks to predict core targets, and related pathways were predicted through GO and KEGG enrichment analysis. The experimental results were verified by the in vitro experiments. HD was applied on AGS/L-OHP cells, and then cellular chemosensitivity and the expressions of P-gp, Survivin, Bcl-2, p-Akt, and p-PI3K genes were detected. Wound assay and Transwell Chamber assay were employed to detect the effect of HD on AGS/L-OHP cells. Nude mice xenograft models transfected using AGS/L-OHP cells were also treated with HD in order to verify the results. The size and weight of the tumor, as well as the expressions of P-gp, Survivin, Bcl-2, p- Akt and p-PI3K genes, were also measured.</p><p><strong>Results: </strong>KEGG analysis showed that the anti-gastric cancer effect of HD was mediated mainly by PI3K-Akt signaling pathways. The PI3K-Akt signaling pathway containing more enriched genes may play a greater role in anti-gastric cancer. It was observed that for AGS/L-OHP cells jointly treated with HD and L-OHP, their activity, migration and invasion were significantly lower than those treated only using HD or L-OHP group. Moreover, expressions of p-Akt, p- PI3K, Bcl-2, P-gp, and Survivin for the HD+L-OHP group decreased significantly. Results of the in vivo experiments showed that the sizes and weights of tumors in the HD+L-OHP group were the lowest compared to the HD group and L-OHP group.</p><p><strong>Conclusion: </strong>Our findings suggest that HD may reduce the resistance of AGS/L-OHP cells to LOHP by regulating the PI3K/Akt signaling pathway.</p>\",\"PeriodicalId\":93961,\"journal\":{\"name\":\"Current computer-aided drug design\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-01-11\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Current computer-aided drug design\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.2174/0115734099270389240104050955\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current computer-aided drug design","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2174/0115734099270389240104050955","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
摘要
目的和目标：本研究旨在通过网络药理学结合实验验证，评估赫达瑞林（Hederagenin，HD）联合奥沙利铂（L-OHP）治疗胃癌（GC）的药理机制：采用网络药理学方法从公共数据库中筛选HD、L-OHP和GC相关靶点的潜在靶点，并提取三个基因集的交叉点。通过蛋白质-蛋白质相互作用（PPI）网络分析交叉基因，预测核心靶点，并通过GO和KEGG富集分析预测相关通路。实验结果经体外实验验证。将 HD 应用于 AGS/L-OHP 细胞，然后检测细胞化学敏感性和 P-gp、Survivin、Bcl-2、p-Akt 和 p-PI3K 基因的表达。采用伤口试验和 Transwell 室试验检测 HD 对 AGS/L-OHP 细胞的影响。为了验证结果，还对转染了 AGS/L-OHP 细胞的裸鼠异种移植模型进行了 HD 处理。此外，还测定了肿瘤的大小和重量，以及 P-gp、Survivin、Bcl-2、p- Akt 和 p-PI3K 基因的表达：KEGG分析表明，HD的抗胃癌作用主要由PI3K-Akt信号通路介导。含有更多富集基因的 PI3K-Akt 信号通路可能在抗胃癌中发挥更大作用。研究发现，联合使用HD和L-OHP处理的AGS/L-OHP细胞，其活性、迁移和侵袭能力明显低于仅使用HD或L-OHP组。此外，HD+L-OHP 组的 p-Akt、p- PI3K、Bcl-2、P-gp 和 Survivin 的表达也明显下降。体内实验结果显示，与 HD 组和 L-OHP 组相比，HD+L-OHP 组的肿瘤大小和重量最小：我们的研究结果表明，HD可通过调节PI3K/Akt信号通路降低AGS/L-OHP细胞对LOHP的耐药性。
Molecular Mechanism Analysis of the Effect of Hederagenin Combined with L-OHP on Chemosensitivity of AGS/L-OHP Based on Network Pharmacology.
Aims and objectives: This study aimed to evaluate the pharmacological mechanism of Hederagenin (HD) combined with oxaliplatin (L-OHP) in treating gastric cancer (GC) through network pharmacology combined with experimental verification.
Material and methods: Network pharmacology methods were used to screen potential targets for HD, L-OHP, and GC-related targets from public databases, and the intersection of the three gene sets was taken. Cross genes were analyzed through protein-protein interaction (PPI) networks to predict core targets, and related pathways were predicted through GO and KEGG enrichment analysis. The experimental results were verified by the in vitro experiments. HD was applied on AGS/L-OHP cells, and then cellular chemosensitivity and the expressions of P-gp, Survivin, Bcl-2, p-Akt, and p-PI3K genes were detected. Wound assay and Transwell Chamber assay were employed to detect the effect of HD on AGS/L-OHP cells. Nude mice xenograft models transfected using AGS/L-OHP cells were also treated with HD in order to verify the results. The size and weight of the tumor, as well as the expressions of P-gp, Survivin, Bcl-2, p- Akt and p-PI3K genes, were also measured.
Results: KEGG analysis showed that the anti-gastric cancer effect of HD was mediated mainly by PI3K-Akt signaling pathways. The PI3K-Akt signaling pathway containing more enriched genes may play a greater role in anti-gastric cancer. It was observed that for AGS/L-OHP cells jointly treated with HD and L-OHP, their activity, migration and invasion were significantly lower than those treated only using HD or L-OHP group. Moreover, expressions of p-Akt, p- PI3K, Bcl-2, P-gp, and Survivin for the HD+L-OHP group decreased significantly. Results of the in vivo experiments showed that the sizes and weights of tumors in the HD+L-OHP group were the lowest compared to the HD group and L-OHP group.
Conclusion: Our findings suggest that HD may reduce the resistance of AGS/L-OHP cells to LOHP by regulating the PI3K/Akt signaling pathway.
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