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Published on: May 3, 2021
Synergistic effect of growth factor receptor-bound protein 2/epidermal growth factor receptor dual-targeting peptide
Zuochong Yu1, Yanlong Xu2, Longhai Du2
1Department of Orthopedics, Huashan Hospital of Fudan University; Department of Orthopedics, Jinshan Hospital of Fudan University, Shanghai, China.
Context:
The growth factor receptor-bound protein 2 (Grb2)-Sos1 interaction, mediated by modular domains, plays an essential role in the oncogenic MAPK signaling pathway in osteosarcoma (OS). Recently, a dual-targeting peptide that targets the epidermal growth factor receptor and Grb2-Src homology 3 domain in OS cells was designed and synthesized.
Aims:
We investigated the synergistic effects of the peptide and salinomycin (Sal), a chemotherapeutic drug with effective anti-OS properties in clinical therapy.
Subjects And Methods:
Flow cytometry was used to measure the targeting efficacy of the peptide. Migration and CCK-8 assays were used to explore whether Sal and the peptide could synergistically inhibit OS cell behavior. Western blotting was used to detect apoptosis.
Statistical Analysis Used:
Data were analyzed using the GraphPad Prism 5.01. Statistical analysis was performed using the Student's t-test for the direct comparisons and one-way analysis of variance for the comparisons among the multiple groups. Statistical significance was set at P < 0.05.
Results:
The peptide was shown to target OS cells. When applied together, Sal and the peptide synergistically inhibited OS cell migration, invasion, and proliferation through the inhibition of Grb2-Sos1. This synergistic treatment also promoted the apoptosis of OS cells and inhibited tumor volume in vivo.
Conclusions:
These data provide valuable insights into the molecular mechanisms of OS and may be beneficial in clinical therapy.
Insights
A novel peptide combined with salinomycin (Sal) synergistically targets osteosarcoma (OS) cells. This combination therapy inhibits tumor growth, migration, and proliferation by blocking the Grb2-Sos1 interaction, offering potential for clinical treatment.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- The Grb2-Sos1 interaction is crucial for the MAPK signaling pathway in osteosarcoma (OS).
- A dual-targeting peptide has been developed to target epidermal growth factor receptor and Grb2-Src homology 3 domain in OS cells.
Purpose of the Study:
- To investigate the synergistic effects of a novel peptide and salinomycin (Sal) in treating osteosarcoma.
- To evaluate the peptide's targeting efficacy and the combined therapy's impact on OS cell behavior.
Main Methods:
- Flow cytometry for peptide targeting efficacy.
- Migration, CCK-8, and Western blotting assays for cell behavior and apoptosis.
- In vivo studies to assess tumor volume inhibition.
Main Results:
- The peptide effectively targeted OS cells.
- Sal and peptide combination synergistically inhibited OS cell migration, invasion, and proliferation by targeting Grb2-Sos1.
- The synergistic treatment promoted OS cell apoptosis and reduced tumor volume in vivo.
Conclusions:
- The combined therapy of Sal and the peptide demonstrates significant synergistic anti-OS effects.
- This approach provides valuable insights into OS molecular mechanisms.
- The findings suggest potential clinical benefits for osteosarcoma treatment.
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