Metformin displays in vitro and in vivo antitumor effect against osteosarcoma.

Bibliographic Details
Title: Metformin displays in vitro and in vivo antitumor effect against osteosarcoma.
Authors: Yunmi Ko, Jun Ah Lee, Aery Choi, Minyoung Lee
Source: Korean Journal of Pediatrics; Sep2016, Vol. 59 Issue 9, p374-380, 7p, 5 Graphs
Subject Terms: METFORMIN, ANTINEOPLASTIC agents, OSTEOSARCOMA, THERAPEUTICS
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. [ABSTRACT FROM AUTHOR]
Copyright of Korean Journal of Pediatrics is the property of Korean Pediatric Society and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Label: Title
  Group: Ti
  Data: Metformin displays in vitro and in vivo antitumor effect against osteosarcoma.
– Name: Author
  Label: Authors
  Group: Au
  Data: <searchLink fieldCode="AR" term="%22Yunmi+Ko%22">Yunmi Ko</searchLink><br /><searchLink fieldCode="AR" term="%22Jun+Ah+Lee%22">Jun Ah Lee</searchLink><br /><searchLink fieldCode="AR" term="%22Aery+Choi%22">Aery Choi</searchLink><br /><searchLink fieldCode="AR" term="%22Minyoung+Lee%22">Minyoung Lee</searchLink>
– Name: TitleSource
  Label: Source
  Group: Src
  Data: Korean Journal of Pediatrics; Sep2016, Vol. 59 Issue 9, p374-380, 7p, 5 Graphs
– Name: Subject
  Label: Subject Terms
  Group: Su
  Data: <searchLink fieldCode="DE" term="%22METFORMIN%22">METFORMIN</searchLink><br /><searchLink fieldCode="DE" term="%22ANTINEOPLASTIC+agents%22">ANTINEOPLASTIC agents</searchLink><br /><searchLink fieldCode="DE" term="%22OSTEOSARCOMA%22">OSTEOSARCOMA</searchLink><br /><searchLink fieldCode="DE" term="%22THERAPEUTICS%22">THERAPEUTICS</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: 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. [ABSTRACT FROM AUTHOR]
– Name: Abstract
  Label:
  Group: Ab
  Data: <i>Copyright of Korean Journal of Pediatrics is the property of Korean Pediatric Society and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.3345/kjp.2016.59.9.374
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      – Code: eng
        Text: English
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        Type: general
      – SubjectFull: ANTINEOPLASTIC agents
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      – TitleFull: Metformin displays in vitro and in vivo antitumor effect against osteosarcoma.
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              M: 09
              Text: Sep2016
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