ORIGINAL ARTICLE |
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Year : 2022 | Volume
: 18
| Issue : 2 | Page : 352-361 |
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Synergistic effect of growth factor receptor-bound protein 2/epidermal growth factor receptor dual-targeting peptide inhibitor and salinomycin on osteosarcoma
Zuochong Yu1, Yanlong Xu2, Longhai Du2, Fan Zhang3, Minghao Shao3, Lin Xie3, Guoping Cai2, Feizhou Lyu3
1 Department of Orthopedics, Huashan Hospital of Fudan University; Department of Orthopedics, Jinshan Hospital of Fudan University, Shanghai, China 2 Department of Orthopedics, Jinshan Hospital of Fudan University, Shanghai, China 3 Department of Orthopedics, Huashan Hospital of Fudan University, Shanghai, China
Correspondence Address:
Feizhou Lyu No. 12, Middle Wulumuqi Road, Shanghai 200040 China Guoping Cai No. 1508, Longhang Road, Shanghai 201508 China
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/jcrt.jcrt_1096_21
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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.
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