Integrated bioinformatic analysis and experiment confirmation of the antagonistic effect and molecular mechanism of ginsenoside Rh2 in metastatic osteosarcoma

Liu, Dan; Wang, Hao; Zhou, Zhangxu; Mao, Xiaohan; Ye, Ziqian; Zhang, Zhilun; Tu, Shixin; Zhang, Yanlai; Cai, Xue; Lan, Xin; Zhang, Zhang; Han, Baoru; Zuo, Guo‐Wei

doi:10.1016/j.jpba.2021.114088

Cited by 6 publications

(4 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PharmMapper Server, based on the effect group stereostructure of drugs, is an important target computing server to screen potential specific targets; it can find the best mapping posture between drug molecules and potential targets. It has been applied to predict targets of treatments in different disease fields, such as compound Salvia miltiorrhiza prescription in the treatment of cardiovascular diseases [ 39 ], trichlorodibenzofuran in the treatment of breast cancer [ 40 ], ginsenoside Rh2 in metastatic osteosarcoma [ 41 ], saffron [ 42 ] and cardamom essential oil [ 43 ]. By means of bioinformatics methods, we found that AZGP1 is the most relevant key target of lenvatinib in ICC.…”

Section: Discussionmentioning

confidence: 99%

AZGP1 activation by lenvatinib suppresses intrahepatic cholangiocarcinoma epithelial-mesenchymal transition through the TGF-β1/Smad3 pathway

Deng,

Bao,

Zhang

et al. 2023

Cell Death Dis

View full text Add to dashboard Cite

Intrahepatic cholangiocarcinoma (ICC) is a primary liver malignancy and is characterized by highly aggressive and malignant biological behavior. Currently, effective treatment strategies are limited. The effect of lenvatinib on ICC is unknown. In this study, we found that AZGP1 was the key target of lenvatinib in ICC, and its low expression in ICC cancer tissues was associated with a poor prognosis in patients. Lenvatinib is a novel AZGP1 agonist candidate for ICC that inhibits ICC-EMT by regulating the TGF-β1/Smad3 signaling pathway in an AZGP1-dependent manner. Furthermore, we found that lenvatinib could increase AZGP1 expression by increasing the acetylation level of H3K27Ac in the promoter region of the AZGP1 gene, thereby inhibiting EMT in ICC cells. In conclusion, lenvatinib activates AZGP1 by increasing the acetylation level of H3K27Ac on the AZGP1 promoter region and regulates the TGF-β1/Smad3 signaling pathway in an AZGP1-dependent manner to inhibit ICC-EMT. This study offers new insight into the mechanism of lenvatinib in the treatment of ICC and provides a theoretical basis for new treatment methods.

show abstract

Section: Discussionmentioning

confidence: 99%

AZGP1 activation by lenvatinib suppresses intrahepatic cholangiocarcinoma epithelial-mesenchymal transition through the TGF-β1/Smad3 pathway

Deng,

Bao,

Zhang

et al. 2023

Cell Death Dis

View full text Add to dashboard Cite

show abstract

“…In OS, treatment with this steroid glycoside led to reduced cell viability and increased the levels of cleaved caspase-3, caspase-8, and caspase-9, while decreasing Bcl-2 levels. Additionally, it promoted the MAPK signaling pathway while inhibiting cell migration and invasion thorough the negative regulation of MMP-2, MMP-7, MMP-9, and mesenchymal markers such as Snail, N-cadherin, and vimentin [ 221 ]. Moreover, when encapsulated in solid silica nanospheres, it reduced tumor volume and recruited immune cells in a murine OS model [ 222 ].…”

Section: Experimental Evidence Nf-κb Inhibitionmentioning

confidence: 99%

Amicis Omnia Sunt Communia: NF-κB Inhibition as an Alternative to Overcome Osteosarcoma Heterogeneity

Medeiros,

Guenka,

Bastos

et al. 2024

Pharmaceuticals

View full text Add to dashboard Cite

Tumor heterogeneity poses a significant challenge in osteosarcoma (OS) treatment. In this regard, the “omics” era has constantly expanded our understanding of biomarkers and altered signaling pathways (i.e., PI3K/AKT/mTOR, WNT/β-catenin, NOTCH, SHH/GLI, among others) involved in OS pathophysiology. Despite different players and complexities, many commonalities have been described, among which the nuclear factor kappa B (NF-κB) stands out. Its altered activation is pervasive in cancer, with pleiotropic action on many disease-relevant traits. Thus, in the scope of this article, we highlight the evidence of NF-κB dysregulation in OS and its integration with other cancer-related pathways while we summarize the repertoire of compounds that have been described to interfere with its action. In silico strategies were used to demonstrate that NF-κB is closely coordinated with other commonly dysregulated signaling pathways not only by functionally interacting with several of their members but also by actively participating in the regulation of their transcription. While existing inhibitors lack selectivity or act indirectly, the therapeutic potential of targeting NF-κB is indisputable, first for its multifunctionality on most cancer hallmarks, and secondly, because, as a common downstream effector of the many dysregulated pathways influencing OS aggressiveness, it turns complex regulatory networks into a simpler picture underneath molecular heterogeneity.

show abstract

“…Up to 25% of the OS cases resulted in metastasis, with pulmonary system being the major site (6). For patients with OS that had lung metastasis, molecules in MAPK signaling pathway and in the PI3K regulatory pathway were abnormally enriched (33). The urokinase plasminogen activator (uPA) is a serine proteinase known to involve in the metastasis of numerous solid tumors.…”

Section: Prognostic Biomarkersmentioning

confidence: 99%

“…Ginsenoside Rh2, a ginseng extract inhibiting the proliferation, migration, and invasion in multiple tumors, has the effect of anti-proliferation and apoptosis-induction in metastatic OS cells and inhibits migration by reversing epithelial-to-mesenchymal transition and promoting degradation of extracellular matrix (33). TRAF2-and NCKinteracting protein kinase (TNIK) was previously recognized as an essential factor of Wnt signaling pathway, whose inhibition leads to the loss of cell stemness.…”

Section: Treatment Evaluationmentioning

confidence: 99%

Application of Multi-Omics Approach in Sarcomas: A Tool for Studying Mechanism, Biomarkers, and Therapeutic Targets

Zou

Sun

et al. 2022

Front. Oncol.

View full text Add to dashboard Cite

Sarcomas are rare, heterogeneous mesenchymal neoplasms with various subtypes, each exhibiting unique genetic characteristics. Although studies have been conducted to improve the treatment for sarcomas, the specific development from normal somatic cells to sarcoma cells is still unclear and needs further research. The diagnosis of sarcomas depends heavily on the pathological examination, which is yet a difficult work and requires expert analysis. Advanced treatment like precise medicine optimizes the efficacy of treatment and the prognosis of sarcoma patients, yet, in sarcomas, more studies should be done to put such methods in clinical practice. The revolution of advanced technology has pushed the multi-omics approach to the front, and more could be learnt in sarcomas with such methods. Multi-omics combines the character of each omics techniques, analyzes the mechanism of tumor cells from different levels, which makes up for the shortage of single-omics, and gives us an integrated picture of bioactivities inside tumor cells. Multi-omics research of sarcomas has reached appreciable progress in recent years, leading to a better understanding of the mutation, proliferation, and metastasis of sarcomas. With the help of multi-omics approach, novel biomarkers were found, with promising effects in improving the process of diagnosis, prognosis anticipation, and treatment decision. By analyzing large amounts of biological features, subtype clustering could be done in a better precision, which may be useful in the clinical procedure. In this review, we summarized recent discoveries using multi-omics approach in sarcomas, discussed their merits and challenges, and concluded with future perspectives of the sarcoma research.

show abstract

Integrated bioinformatic analysis and experiment confirmation of the antagonistic effect and molecular mechanism of ginsenoside Rh2 in metastatic osteosarcoma

Cited by 6 publications

References 44 publications

AZGP1 activation by lenvatinib suppresses intrahepatic cholangiocarcinoma epithelial-mesenchymal transition through the TGF-β1/Smad3 pathway

AZGP1 activation by lenvatinib suppresses intrahepatic cholangiocarcinoma epithelial-mesenchymal transition through the TGF-β1/Smad3 pathway

Amicis Omnia Sunt Communia: NF-κB Inhibition as an Alternative to Overcome Osteosarcoma Heterogeneity

Application of Multi-Omics Approach in Sarcomas: A Tool for Studying Mechanism, Biomarkers, and Therapeutic Targets

Contact Info

Product

Resources

About