Tongguanteng injection reverses paclitaxel resistance via upregulation of TAB1 expression in ovarian cancer in vitro and in vivo

Kong, Qian-Wen; Jiao, Yang; Li, Dan; Ding, Ya-Wei; Hu, Yujie; Xue, Xiao-Chuan; Shi, Mei-Zhi; Jiang, Bo; Zhou, Yang-Yun; Zhang, Min; Hu, Jialei; Guo, Cheng; Chen, Jun–Jun; Han, Yonglong

doi:10.1016/j.jep.2022.115728

Cited by 4 publications

(5 citation statements)

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“…These studies have gained increasing attention from people. TCM preparation TGT exhibits significant therapeutic effects on various tumors, such as triggering cell cycle halt and apoptosis in ovarian cancer [19,25]. Additionally, it synergizes with chemotherapy drugs to enhance the efficacy against gastric cancer while reducing adverse reactions [10].…”

Section: Discussionmentioning

confidence: 99%

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Network pharmacology and experimental validation to study the potential mechanism of Tongguanteng injection in regulating apoptosis in osteosarcoma

Wei,

Meng,

Xiang

et al. 2024

BMC Complement Med Ther

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Objective The main objectives of this study were to identify the active components of Tongguanteng injection (TGT) and investigate the preclinical efficacy and mechanism of TGT on osteosarcoma using a combination of network pharmacology and experimental validation. Methods To identify the active constituents and targets of TGT against osteosarcoma using network pharmacology, we constructed a network consisting of an 'active ingredient-disease-target-pathway' and a protein–protein interaction (PPI) network. The target organ network was utilized to investigate the distribution of core targets in tissues. Afterwards, the core targets underwent Gene ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The binding energy between receptors and ligands was compared using molecular docking. In addition, SwissADME was employed to forecast the pharmacokinetic characteristics of the substances. Finally, real-time polymerase chain reaction (RT-PCR), cell proliferation assay, morphological analysis, apoptosis assay, mitochondrial membrane potential (MMP) detection, and Western blotting were utilized to confirm the potential mechanisms of TGT treatment in osteosarcoma cell lines 143B and SAOS2. Results A total of 54 chemical constituents of TGT and 71 targets associated with osteosarcoma were acquired. Through the molecular docking technology, Tenacigenin B, Marsdekoiside, Taraxasterol, Tenacissoside G, Tenacissoside L, and Tenacissoside J were identified as the primary active components of TGT among the various compounds. Analysis of target organs suggests that TGT may play an anti-osteosarcoma role through immune regulation. The GO and KEGG enrichment analysis revealed that TGT could trigger osteosarcoma cell apoptosis by inhibiting the HIF-1 signalling pathway and modulating PD-1 expression and the PD-1 checkpoint pathway in cancer. SwissADME database predicted that Tenacigenin B and Taraxasterol had the best drug-likeness. In vitro studies also demonstrated that TGT suppressed the activity and induced alterations in the morphology of osteosarcoma cells. It decreased MMP levels, triggered apoptosis by increasing Bax expression and Caspase-3 activity, and decreased Bcl-2 expression, thereby exerting an anti-osteosarcoma effect. In the meantime, RT-PCR tests demonstrated that TGT could control immune response against tumors and hinder the proliferation and spread of cancerous cells by impacting the levels of critical factors, including JUN, HSP90AA1, HDAC1, and CDK1. Conclusion The study accurately anticipated the active components, targets, and pathways of TGT in the management of osteosarcoma. The molecular mechanism of TGT-induced apoptosis in osteosarcoma cells was demonstrated by in vitro experiments. These results provide theoretical and technical support for TGT as a clinical adjuvant drug for osteosarcoma.

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Section: Discussionmentioning

confidence: 99%

“…Wight et Arn. stem was extracted as previously described [19]. The TGT manufacturing process was prepared following the standard of the 2020 edition of Pharmacopoeia of The People's Republic of China (Ch.P.)…”

Section: Chemicals and Reagentsmentioning

confidence: 99%

Network pharmacology and experimental validation to study the potential mechanism of Tongguanteng injection in regulating apoptosis in osteosarcoma

Wei,

Meng,

Xiang

et al. 2024

BMC Complement Med Ther

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show abstract

“…These studies have gained increasing attention from people. TCM preparation TGT exhibits signi cant therapeutic effects on various tumors, such as triggering cell cycle halt and apoptosis in ovarian cancer [20,21]. Additionally, it synergizes with chemotherapy drugs to enhance the e cacy against gastric cancer while reducing adverse reactions [10].…”

Section: Discussionmentioning

confidence: 99%

“…Wight et Arn. stem was extracted as previously described (Kong et al, 2023). The TGT manufacturing process was prepared following the standard of 2020 edition of Pharmacopoeia of The People's Republic of China (Ch.P.)…”

Section: Chemicals and Reagentsmentioning

confidence: 99%

Network pharmacology and experimental validation to study the potential mechanism of Tongguanteng injection against osteosarcoma

Wei,

meng,

xiang

et al. 2023

Preprint

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Objective The main objectives of this study were to identify the active components of TGT and investigate the preclinical efficacy and mechanism of TGT on osteosarcoma using a combination of network pharmacology and experimental validation. Methods To identify the active constituents and targets of TGT against osteosarcoma using network pharmacology, we constructed a network consisting of an 'active ingredient-disease-target-pathway' and a protein-protein interaction (PPI) network. The target organ network was utilized to investigate the distribution of core targets in tissues. Afterward, the core targets underwent Gene ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The comparison of binding energy between receptors and ligands was conducted using molecular docking. In addition, SwissADME was employed to forecast the pharmacokinetic characteristics of the substances. Finally, real-time polymerase chain reaction (RT-PCR), cell proliferation assay, morphological analysis, apoptosis assay, mitochondrial membrane potential (MMP) detection, and Western Blotting were utilized to confirm the potential mechanisms of TGT treatment in osteosarcoma cell lines 143B and SAOS2. Results A total of 54 chemical constituents of TGT and 71 targets associated with osteosarcoma were acquired. Through the molecular docking technology, Tenacigenin B, Marsdekoiside, Taraxasterol, Tenacissoside G, Tenacissoside L, and Tenacissoside J were identified as the primary active components of TGT among the various compounds. Analysis of target organs suggests that TGT may play an anti-osteosarcoma role through immune regulation. The analysis of GO and KEGG enrichment revealed that TGT can trigger osteosarcoma cell apoptosis by inhibiting the HIF-1 signaling pathway and modulating PD-1 expression and the PD-1 checkpoint pathway in cancer. SwissADME database predicted that Tenacigenin B and Taraxasterol had the best drug-likeness. In vitro studies also demonstrated that TGT suppressed the activity and induced alterations in the morphology of osteosarcoma cells. It decreased MMP levels, triggered apoptosis by increasing Bax expression and Caspase-3 activity, and decreased Bcl-2 expression, thereby exerting an anti-osteosarcoma effect. In the meantime, RT-PCR tests demonstrated that TGT can control immune response against tumors and hinder the proliferation and spread of cancerous cells through its impact on the levels of key factors including JUN, HSP90AA1, HDAC1, and CDK1. Conclusion The study accurately anticipated the active components, targets, and pathways of TGT in the management of osteosarcoma. The molecular mechanism of TGT induced apoptosis in osteosarcoma cells was demonstrated by in vitro experiments. These results provide theoretical and technical support for TGT as a clinical adjuvant drug for osteosarcoma.

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“…This drug also inhibits the effects of other factors on the microtubule system and, together with the stable binding of microtubule proteins, eventually induces apoptosis ( Liu et al, 2017a ). In clinical applications, paclitaxel has shown good efficacy in treating non-small cell lung cancer ( Hoang et al, 2012 ), breast cancer ( Manhas et al, 2022 ), gastric cancer ( Tu et al, 2022 ), nasopharyngeal cancer ( Xia et al, 2022 ), ovarian cancer ( Kong et al, 2023 )and cervical cancer ( Yasunaga et al, 2022 ), particularly for drug-resistant tumors ( Song et al, 2018 ; Kawiak et al, 2019 ). Although the therapeutic efficacy of paclitaxel in glioma has been confirmed, its therapeutic mechanism remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Mechanism of action of paclitaxel for treating glioblastoma based on single-cell RNA sequencing data and network pharmacology

Rao

et al. 2022

Front. Pharmacol.

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Paclitaxel is an herbal active ingredient used in clinical practice that shows anti-tumor effects. However, its biological activity, mechanism, and cancer cell-killing effects remain unknown. Information on the chemical gene interactions of paclitaxel was obtained from the Comparative Toxicogenomics Database, SwishTargetPrediction, Binding DB, and TargetNet databases. Gene expression data were obtained from the GSE4290 dataset. Differential gene analysis, Kyoto Encyclopedia of Genes and Genomes, and Gene Ontology analyses were performed. Gene set enrichment analysis was performed to evaluate disease pathway activation; weighted gene co-expression network analysis with diff analysis was used to identify disease-associated genes, analyze differential genes, and identify drug targets via protein-protein interactions. The Molecular Complex Detection (MCODE) analysis of critical subgroup networks was conducted to identify essential genes affected by paclitaxel, assess crucial cluster gene expression differences in glioma versus standard samples, and perform receiver operator characteristic mapping. To evaluate the pharmacological targets and signaling pathways of paclitaxel in glioblastoma, the single-cell GSE148196 dataset was acquired from the Gene Expression Omnibus database and preprocessed using Seurat software. Based on the single-cell RNA-sequencing dataset, 24 cell clusters were identified, along with marker genes for the two different cell types in each cluster. Correlation analysis revealed that the mechanism of paclitaxel treatment involves effects on neurons. Paclitaxel may affect glioblastoma by improving glucose metabolism and processes involved in modulating immune function in the body.

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Tongguanteng injection reverses paclitaxel resistance via upregulation of TAB1 expression in ovarian cancer in vitro and in vivo

Cited by 4 publications

References 42 publications

Network pharmacology and experimental validation to study the potential mechanism of Tongguanteng injection in regulating apoptosis in osteosarcoma

Network pharmacology and experimental validation to study the potential mechanism of Tongguanteng injection in regulating apoptosis in osteosarcoma

Network pharmacology and experimental validation to study the potential mechanism of Tongguanteng injection against osteosarcoma

Mechanism of action of paclitaxel for treating glioblastoma based on single-cell RNA sequencing data and network pharmacology

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