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Updated: May 6, 2026
A Syngeneic Orthotopic Osteosarcoma Sprague Dawley Rat Model with Amputation to Control Metastasis Rate
Published on: May 3, 2021
Integrating network pharmacology and transcriptomics to identify solasonine's anti-osteosarcoma targets and
Daihao Wei1,2, Minyu Li2, Dawei Chu2
1Department of Orthopedic, General Hospital of Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region, China.
Background:
Osteosarcoma (OS) patients face the challenge of having few effective therapeutic drugs. Solasonine(SS)is an active component of TCM against OS cells. This study aims to identify the key targets of solasonine in treating OS.
Methods:
In this study, the transcriptome data and related gene sets were first downloaded from public databases. Subsequently, candidate targets were obtained by intersecting differentially expressed genes (DEGs) with solasonine and OS disease targets. Key targets were then identified through regression analyses, and a prognostic model was constructed. A nomogram was subsequently constructed using the key targets. The functions and immune microenvironment, as well as the structure, regulatory network, and molecular docking of these key targets, were then analyzed. The expression level of the candidate targets in osteosarcoma cells was verified in RT-qPCR experiments, and the effect of solasonine on the malignant biological behavior of osteosarcoma cells was verified.
Results:
DEGs, targets corresponding to solasonine, and OS-related disease targets were intersected to obtain 37 candidate targets. Subsequent regression analyses identified 5 key targets (ATP1A1, CLK1, SIGMAR1, PYGM, HSP90B1). It was further demonstrated that the OS prognostic model constructed using these key targets was robust. The constructed nomogram provided an excellent predictive model. Moreover, some pathways, such as cytokine-cytokine receptor interaction, were significantly enriched, and there were 4 significantly different immune cells and 3 significantly different immune checkpoints (P<0.05). Additionally, natural killer cells and activated B cells were significantly positively correlated (cor = 0.68, P < 0.001). The subsequent regulatory network included transcription factors regulating the 5 targets. All key targets showed favorable molecular docking effects with SS. The target genes all exhibited higher expression in osteosarcoma cell lines(P<0.05). Solasonine can inhibit the malignant biological behavior of cell proliferation, migration and invasion.
Conclusion:
In this study, ATP1A1, CLK1, SIGMAR1, PYGM, and HSP90B1 were identified as key targets of solasonine in the treatment of OS, and they were found to have reference significance for the treatment of OS. SS can be a potential drug for the treatment of osteosarcoma.
Insights
Solasonine, a traditional Chinese medicine component, shows promise for treating osteosarcoma (OS). Researchers identified five key targets (ATP1A1, CLK1, SIGMAR1, PYGM, HSP90B1) that solasonine affects, offering new therapeutic avenues for OS.
Area of Science:
- Oncology
- Pharmacology
- Genomics
Background:
- Osteosarcoma (OS) presents a significant challenge due to limited effective therapeutic options.
- Solasonine (SS), a component of traditional Chinese medicine (TCM), exhibits activity against OS cells.
Purpose of the Study:
- To identify the key molecular targets of solasonine in the treatment of osteosarcoma.
- To validate the therapeutic potential of solasonine for osteosarcoma.
Main Methods:
- Transcriptome data analysis to identify differentially expressed genes (DEGs) in OS.
- Intersection of DEGs with solasonine and OS targets to identify candidate and key targets.
- Construction and validation of a prognostic model and nomogram based on key targets.
- Analysis of key target functions, immune microenvironment, regulatory networks, and molecular docking with solasonine.
Main Results:
- Five key targets (ATP1A1, CLK1, SIGMAR1, PYGM, HSP90B1) were identified through regression analyses.
- A robust prognostic model and predictive nomogram were constructed using these key targets.
- Significant enrichment in pathways like cytokine-cytokine receptor interaction and distinct immune cell profiles were observed.
- Solasonine demonstrated inhibition of osteosarcoma cell proliferation, migration, and invasion in experimental models.
Conclusions:
- ATP1A1, CLK1, SIGMAR1, PYGM, and HSP90B1 are identified as key targets for solasonine in osteosarcoma treatment.
- These targets hold significant reference value for developing novel osteosarcoma therapies.
- Solasonine emerges as a potential therapeutic agent for osteosarcoma.
