<it>In vitro</it> and <it>in vivo</it> anti-tumor effect of metformin as a novel therapeutic agent in human oral squamous cell carcinoma
<p>Abstract</p> <p>Background</p> <p>Metformin, which is widely used as an antidiabetic agent, has recently been reported to reduce cancer risk and improve prognosis in certain malignancies. However, the specific mechanisms underlying the effect of metformin on the deve...
Main Authors: | , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
BMC
2012-11-01
|
Series: | BMC Cancer |
Subjects: | |
Online Access: | http://www.biomedcentral.com/1471-2407/12/517 |
id |
doaj-6c4156d190ce4153a5c42bfed480e679 |
---|---|
record_format |
Article |
spelling |
doaj-6c4156d190ce4153a5c42bfed480e6792020-11-25T01:57:22ZengBMCBMC Cancer1471-24072012-11-0112151710.1186/1471-2407-12-517<it>In vitro</it> and <it>in vivo</it> anti-tumor effect of metformin as a novel therapeutic agent in human oral squamous cell carcinomaLuo QingqiongHu DanHu ShuiqingYan MingSun ZujunChen Fuxiang<p>Abstract</p> <p>Background</p> <p>Metformin, which is widely used as an antidiabetic agent, has recently been reported to reduce cancer risk and improve prognosis in certain malignancies. However, the specific mechanisms underlying the effect of metformin on the development and progression of several cancers including oral squamous cell carcinoma (OSCC) remain unclear. In the present study, we investigated the effects of metformin on OSCC cells <it>in vitro</it> and <it>in vivo</it>.</p> <p>Methods</p> <p>OSCC cells treated with or without metformin were counted using a hemocytometer. The clonogenic ability of OSCC cells after metformin treatment was determined by colony formation assay. Cell cycle progression and apoptosis were assessed by flow cytometry, and the activation of related signaling pathways was examined by immunoblotting. The <it>in vivo</it> anti-tumor effect of metformin was examined using a xenograft mouse model. Immunohistochemistry and TUNEL staining were used to determine the expression of cyclin D1 and the presence of apoptotic cells in tumors from mice treated with or without metformin.</p> <p>Results</p> <p>Metformin inhibited proliferation in the OSCC cell lines CAL27, WSU-HN6 and SCC25 in a time- and dose-dependent manner, and significantly reduced the colony formation of OSCC cells <it>in vitro.</it> Metformin induced an apparent cell cycle arrest at the G0/G1 phase, which was accompanied by an obvious activation of the AMP kinase pathway and a strongly decreased activation of mammalian target of rapamycin and S6 kinase. Metformin treatment led to a remarkable decrease of cyclin D1, cyclin-dependent kinase (CDK) 4 and CDK6 protein levels and phosphorylation of retinoblastoma protein, but did not affect p21 or p27 protein expression in OSCC cells. In addition, metformin induced apoptosis in OSCC cells, significantly down-regulating the anti-apoptotic proteins Bcl-2 and Bcl-xL and up-regulating the pro-apoptotic protein Bax. Metformin also markedly reduced the expression of cyclin D1 and increased the numbers of apoptotic cells <it>in vivo</it>, thus inhibiting the growth of OSCC xenografts.</p> <p>Conclusions</p> <p>Our data suggested that metformin could be a potential candidate for the development of new treatment strategies for human OSCC.</p> http://www.biomedcentral.com/1471-2407/12/517MetforminOral squamous cell carcinomasCell cycleCyclin D1Apoptosis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Luo Qingqiong Hu Dan Hu Shuiqing Yan Ming Sun Zujun Chen Fuxiang |
spellingShingle |
Luo Qingqiong Hu Dan Hu Shuiqing Yan Ming Sun Zujun Chen Fuxiang <it>In vitro</it> and <it>in vivo</it> anti-tumor effect of metformin as a novel therapeutic agent in human oral squamous cell carcinoma BMC Cancer Metformin Oral squamous cell carcinomas Cell cycle Cyclin D1 Apoptosis |
author_facet |
Luo Qingqiong Hu Dan Hu Shuiqing Yan Ming Sun Zujun Chen Fuxiang |
author_sort |
Luo Qingqiong |
title |
<it>In vitro</it> and <it>in vivo</it> anti-tumor effect of metformin as a novel therapeutic agent in human oral squamous cell carcinoma |
title_short |
<it>In vitro</it> and <it>in vivo</it> anti-tumor effect of metformin as a novel therapeutic agent in human oral squamous cell carcinoma |
title_full |
<it>In vitro</it> and <it>in vivo</it> anti-tumor effect of metformin as a novel therapeutic agent in human oral squamous cell carcinoma |
title_fullStr |
<it>In vitro</it> and <it>in vivo</it> anti-tumor effect of metformin as a novel therapeutic agent in human oral squamous cell carcinoma |
title_full_unstemmed |
<it>In vitro</it> and <it>in vivo</it> anti-tumor effect of metformin as a novel therapeutic agent in human oral squamous cell carcinoma |
title_sort |
<it>in vitro</it> and <it>in vivo</it> anti-tumor effect of metformin as a novel therapeutic agent in human oral squamous cell carcinoma |
publisher |
BMC |
series |
BMC Cancer |
issn |
1471-2407 |
publishDate |
2012-11-01 |
description |
<p>Abstract</p> <p>Background</p> <p>Metformin, which is widely used as an antidiabetic agent, has recently been reported to reduce cancer risk and improve prognosis in certain malignancies. However, the specific mechanisms underlying the effect of metformin on the development and progression of several cancers including oral squamous cell carcinoma (OSCC) remain unclear. In the present study, we investigated the effects of metformin on OSCC cells <it>in vitro</it> and <it>in vivo</it>.</p> <p>Methods</p> <p>OSCC cells treated with or without metformin were counted using a hemocytometer. The clonogenic ability of OSCC cells after metformin treatment was determined by colony formation assay. Cell cycle progression and apoptosis were assessed by flow cytometry, and the activation of related signaling pathways was examined by immunoblotting. The <it>in vivo</it> anti-tumor effect of metformin was examined using a xenograft mouse model. Immunohistochemistry and TUNEL staining were used to determine the expression of cyclin D1 and the presence of apoptotic cells in tumors from mice treated with or without metformin.</p> <p>Results</p> <p>Metformin inhibited proliferation in the OSCC cell lines CAL27, WSU-HN6 and SCC25 in a time- and dose-dependent manner, and significantly reduced the colony formation of OSCC cells <it>in vitro.</it> Metformin induced an apparent cell cycle arrest at the G0/G1 phase, which was accompanied by an obvious activation of the AMP kinase pathway and a strongly decreased activation of mammalian target of rapamycin and S6 kinase. Metformin treatment led to a remarkable decrease of cyclin D1, cyclin-dependent kinase (CDK) 4 and CDK6 protein levels and phosphorylation of retinoblastoma protein, but did not affect p21 or p27 protein expression in OSCC cells. In addition, metformin induced apoptosis in OSCC cells, significantly down-regulating the anti-apoptotic proteins Bcl-2 and Bcl-xL and up-regulating the pro-apoptotic protein Bax. Metformin also markedly reduced the expression of cyclin D1 and increased the numbers of apoptotic cells <it>in vivo</it>, thus inhibiting the growth of OSCC xenografts.</p> <p>Conclusions</p> <p>Our data suggested that metformin could be a potential candidate for the development of new treatment strategies for human OSCC.</p> |
topic |
Metformin Oral squamous cell carcinomas Cell cycle Cyclin D1 Apoptosis |
url |
http://www.biomedcentral.com/1471-2407/12/517 |
work_keys_str_mv |
AT luoqingqiong itinvitroitanditinvivoitantitumoreffectofmetforminasanoveltherapeuticagentinhumanoralsquamouscellcarcinoma AT hudan itinvitroitanditinvivoitantitumoreffectofmetforminasanoveltherapeuticagentinhumanoralsquamouscellcarcinoma AT hushuiqing itinvitroitanditinvivoitantitumoreffectofmetforminasanoveltherapeuticagentinhumanoralsquamouscellcarcinoma AT yanming itinvitroitanditinvivoitantitumoreffectofmetforminasanoveltherapeuticagentinhumanoralsquamouscellcarcinoma AT sunzujun itinvitroitanditinvivoitantitumoreffectofmetforminasanoveltherapeuticagentinhumanoralsquamouscellcarcinoma AT chenfuxiang itinvitroitanditinvivoitantitumoreffectofmetforminasanoveltherapeuticagentinhumanoralsquamouscellcarcinoma |
_version_ |
1724974552120819712 |