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KMID : 1130320160590090374
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Korean Journal of Pediatrics
2016 Volume.59 No. 9 p.374 ~ p.380
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Metformin displays in vitro and in vivo antitumor effect against osteosarcoma
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Ko Yun-Mi
Choi Ae-Ry
Lee Min-Young
Lee Jun-Ah
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Abstract
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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.
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KEYWORD
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Metformin, Osteosarcoma, Antitumor effect
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