Metformin displays in vitro and in vivo antitumor effect against osteosarcoma.
10.3345/kjp.2016.59.9.374
- Author:
Yunmi KO
1
;
Aery CHOI
;
Minyoung LEE
;
Jun Ah LEE
Author Information
1. Division of Clinical Translational Research, Korea Cancer Center Hospital, Seoul, Korea. junahlee@kcch.re.kr
- Publication Type:Original Article
- Keywords:
Metformin;
Osteosarcoma;
Antitumor effect
- MeSH:
AMP-Activated Protein Kinases;
Animals;
Apoptosis;
Cell Cycle;
Cell Line;
Cell Proliferation;
Clone Cells;
Female;
Heterografts;
Humans;
In Vitro Techniques*;
Metformin*;
Mice;
Osteosarcoma*;
Sirolimus;
Thigh;
Transplants;
Tumor Burden;
Water;
Wound Healing
- From:Korean Journal of Pediatrics
2016;59(9):374-380
- CountryRepublic of Korea
- Language:English
-
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.
