Metformin displays in vitro and in vivo antitumor effect against osteosarcoma / 소아과
Korean Journal of Pediatrics
;
: 374-380, 2016.
Article
in English
| WPRIM
| ID: wpr-155948
ABSTRACT
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Thigh
/
Wound Healing
/
In Vitro Techniques
/
Water
/
Osteosarcoma
/
Cell Cycle
/
Cell Line
/
Clone Cells
/
Apoptosis
/
Transplants
Limits:
Animals
/
Female
/
Humans
Language:
English
Journal:
Korean Journal of Pediatrics
Year:
2016
Type:
Article
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