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Metformin displays in vitro and in vivo antitumor effect against osteosarcoma
Yunmi Ko1, Aery Choi2, Minyoung Lee3
1Division of Clinical Translational Research, Korea Cancer Center Hospital, Seoul, Korea.
Purpose:
Patients with unresectable, relapsed, or refractory osteosarcoma need a novel therapeutic agent. Metformin is a biguanide derivative used in the treatment of type II diabetes, and is recently gaining attention in cancer research.
Methods:
We evaluated the effect of metformin against human osteosarcoma. Four osteosarcoma cell lines (KHOS/NP, HOS, MG-63, U-2 OS) were treated with metformin and cell proliferation was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell cycle progression and apoptosis were evaluated using flow cytometric analysis, and migration and wound healing assay were performed. Fourteen female Balb/c-nude mice received KHOS/NP cell grafts in their thigh, and were allowed access to metformin containing water (2 mg/mL) ad libitum. Tumor volume was measured every 3-4 days for a period of 4 weeks.
Results:
Metformin had a significant antiproliferative effect on human osteosarcoma cells. In particular, metformin inhibited the proliferation and migration of KHOS/NP cells by activation of AMP-activated protein kinase and consequent inhibition of the mammalian target of rapamycin pathway. It also inhibited the proliferation of cisplatin-resistant KHOS/NP clone cells. Analysis of KHOS/NP xenograft Balb/c-nude models indicated that metformin displayed potent in vivo antitumor effects.
Conclusion:
Further studies are necessary to explore metformin's therapeutic potential and the possibilities for its use as an adjuvant agent for osteosarcoma.
Insights
Metformin, a diabetes drug, effectively inhibited osteosarcoma cell growth and migration in preclinical studies. This suggests metformin
Area of Science:
- Oncology
- Pharmacology
- Biochemistry
Background:
- Osteosarcoma is a challenging bone cancer with limited treatment options for unresectable or refractory cases.
- Metformin, a common type 2 diabetes medication, is being investigated for its potential anticancer properties.
Purpose of the Study:
- To evaluate the efficacy of metformin as a therapeutic agent against human osteosarcoma.
- To investigate the molecular mechanisms underlying metformin's effects on osteosarcoma cells.
Main Methods:
- In vitro studies involved treating four human osteosarcoma cell lines with metformin, assessing proliferation, cell cycle, apoptosis, and migration.
- In vivo studies utilized a mouse xenograft model implanted with KHOS/NP cells to evaluate metformin's antitumor effects.
Main Results:
- Metformin demonstrated significant antiproliferative and antimigratory effects on human osteosarcoma cells, particularly KHOS/NP.
- The drug's action involved activating AMP-activated protein kinase (AMPK) and inhibiting the mammalian target of rapamycin (mTOR) pathway.
- Metformin also inhibited cisplatin-resistant osteosarcoma cells and showed potent in vivo antitumor activity in a mouse model.
Conclusions:
- Metformin exhibits promising therapeutic potential for osteosarcoma.
- Further research is warranted to explore metformin's use as a standalone or adjuvant therapy for osteosarcoma.
