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ORIGINAL ARTICLE
Year : 2022  |  Volume : 18  |  Issue : 2  |  Page : 352-361

Synergistic effect of growth factor receptor-bound protein 2/epidermal growth factor receptor dual-targeting peptide inhibitor and salinomycin on osteosarcoma


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
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Source of Support: None, Conflict of Interest: None


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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