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Metformin inhibits growth and sensitizes osteosarcoma cell lines to cisplatin through cell cycle modulation
Irene Quattrini1, Amalia Conti, Laura Pazzaglia
1Laboratory of Experimental Oncology, Rizzoli Orthopaedic Institute, I-40136 Bologna, Italy.
Abstract:
Osteosarcoma (OS) is the most common cancer that affects the bone and appears to be resistant to several chemotherapeutic drugs. The aim of the present study was to verify whether the combination of metformin and cisplatin has an effect on OS cell lines. OS cell lines U2OS, 143B and MG63 were treated with metformin, cisplatin or a combination of both drugs. Viability, apoptosis and cell cycle were evaluated to characterize the effects of the treatments. Western blot analyses were used to evaluate protein expression. All OS cell lines were found to be sensitive to metformin with different values of IC50, showing a slowdown of cell cycle associated or not with apoptosis. In particular, metformin was able to sensitize cells to cisplatin, to which all OS cell lines were resistant, demonstrating a synergistic effect in the combined treatment of the two drugs. The data obtained may have clinical relevance for novel therapeutic strategies for the treatment of OS; metformin inhibits tumor cell growth and amplifies the effect of cisplatin.
Insights
Metformin enhances cisplatin
Area of Science:
- Oncology
- Pharmacology
Background:
- Osteosarcoma (OS) is a prevalent bone cancer.
- OS often exhibits resistance to conventional chemotherapy.
Purpose of the Study:
- To investigate the combined effect of metformin and cisplatin on OS cell lines.
- To determine if metformin can overcome cisplatin resistance in OS.
Main Methods:
- Treatment of OS cell lines (U2OS, 143B, MG63) with metformin, cisplatin, or both.
- Evaluation of cell viability, apoptosis, and cell cycle.
- Protein expression analysis via Western blot.
Main Results:
- Metformin demonstrated sensitivity across OS cell lines, impacting cell cycle and apoptosis.
- Metformin sensitized cisplatin-resistant OS cells, indicating a synergistic effect.
- Combined treatment showed enhanced anti-cancer effects.
Conclusions:
- Metformin shows potential as an adjuvant therapy for osteosarcoma.
- Combination therapy with metformin and cisplatin may offer a novel therapeutic strategy for OS.
- Metformin inhibits tumor growth and potentiates cisplatin's efficacy in OS.
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