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Published on: May 3, 2021
Differentially activated Src kinase in chemo-naïve human primary osteosarcoma cells and effects of a Src kinase
Marcella Laschi1, Giulia Bernardini1, Michela Geminiani1
1Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, via A. Moro 2, Siena, 53100, Italy.
Abstract:
The therapeutic treatment of osteosarcoma (OS), a rare malignant teenage cancer of the skeletal system, still represents a great challenge as patient survival after conventional protocol chemotherapy treatment has not improved in the last four decades leaving poor patient prognoses. Therefore, many efforts have been done to find increasingly reliable OS cell models and to identify "druggable" targets in OS, in order to identify novel effective therapeutic approaches and treatment strategies. In this contest, the more successful use of patient-derived cell cultures in respect to human commercial lines and findings of Src kinase deregulation in cancer, prompted us to study for the first time the activation state of Src and the potential activity of our Src inhibitor SI-83 in a number of chemo-naïve patient-derived primary OS cells. We here demonstrate that Src is hyperactivated in OS cells in respect to the nonmalignant counterpart and that SI-83 is able to strongly decrease cell viability, proliferation, Src416 phosphorylation, and cell migration. © 2017 BioFactors, 43(6):801-811, 2017.
Insights
Src kinase is hyperactivated in osteosarcoma (OS), a rare bone cancer. A novel Src inhibitor, SI-83, effectively reduced cancer cell viability, proliferation, and migration in patient-derived models.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- Osteosarcoma (OS) treatment remains challenging, with stagnant survival rates despite conventional chemotherapy.
- There is a critical need for improved OS cell models and identification of novel therapeutic targets.
- Src kinase deregulation is implicated in various cancers, suggesting its potential role in OS.
Purpose of the Study:
- To investigate Src kinase activation in patient-derived osteosarcoma cells.
- To evaluate the efficacy of a novel Src inhibitor, SI-83, in treating chemo-naïve OS.
- To explore SI-83's impact on OS cell viability, proliferation, and migration.
Main Methods:
- Utilized chemo-naïve patient-derived primary osteosarcoma cell cultures.
- Assessed Src kinase activation status and Src416 phosphorylation.
- Administered Src inhibitor SI-83 and measured its effects on cell viability, proliferation, and migration.
Main Results:
- Src kinase was found to be hyperactivated in osteosarcoma cells compared to non-malignant cells.
- SI-83 significantly reduced osteosarcoma cell viability and proliferation.
- SI-83 treatment also decreased Src416 phosphorylation and inhibited cell migration in OS cells.
Conclusions:
- Src kinase is a potential therapeutic target in osteosarcoma.
- The Src inhibitor SI-83 demonstrates significant anti-cancer activity in patient-derived OS models.
- SI-83 represents a promising novel therapeutic strategy for osteosarcoma treatment.
