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1.
Pathol Res Pract ; 213(5): 496-501, 2017 May.
Article in English | MEDLINE | ID: mdl-28285966

ABSTRACT

OBJECTIVE: The purpose of the current study is to investigate the association between E-cadherin methylation status, hypoxia and OSCC. METHODS: HaCat and SCC9 cell lines were submitted to hypoxic treatment, followed by methylation profile analysis (MS-PCR) and analysis of the expression of mRNA gene E-cadherin (RT-PCR). Study group samples comprise individuals affected by potentially malignant lesions Potential Malignant Oral Lesion (PMOL, n=18) and oral squamous cell carcinoma (OSCC, n=28). The control group oral mucosa (OM, n=15) of patients with an oral mucocele. Cell migration ability was evaluated a scratch wound assay in SCC9 and HaCat cell lines RESULTS: E-cadherin mRNA expression in the cell lines SCC9 and HaCat was significantly reduced under hypoxia, regardless of the methylation profile, when compared to the control group. No differences in methylation profile of the E-cadherin were observed among the groups OM, PMOL and OSCC. HaCat and SCC9 presented increases in cell migration rates under hypoxia. CONCLUSION: The current study demonstrates that hypoxia reduces E-cadherin expression and increase cell migration, regardless of the methylation profile. Additionally, no differences in E-cadherin methylation patterns were observed among OM, PMOL and OSCC.


Subject(s)
Cadherins/metabolism , Carcinoma, Squamous Cell/metabolism , Cell Hypoxia , Gene Expression Regulation, Neoplastic , Mouth Neoplasms/metabolism , Antigens, CD , Carcinoma, Squamous Cell/pathology , Cell Line, Tumor , Cell Movement , Humans , Methylation , Mouth Neoplasms/pathology , RNA, Messenger
2.
Oncotarget ; 7(34): 55057-55068, 2016 Aug 23.
Article in English | MEDLINE | ID: mdl-27474170

ABSTRACT

BACKGROUND: Metformin is a biguanide, belonging to the oral hypoglycemic agents and is a widely used in the treatment of type 2 diabetes. Evidence indicate that Metformin inhibits cell proliferation in several human cancers and inhibits the Warburg phenomenon in tumor cells. RESULTS: Low PDH levels were observed in OSCC, and Metformin promotes an increase in PDH levels in hypoxic conditions. Metformin also reduced HIF-1α mRNA and protein levels. Metformin demonstrated antiproliferative effects, inhibited migration, increased the number of apoptotic cells and increased the transcription of caspase 3. OBJECTIVE: The present study aims to explore the effects of Metformin in hypoxic conditions. Specifically, we focused on pyruvate dehydrogenase (PDH), (hypoxia-inducible factor 1α) HIF-1α levels and the oral squamous cell carcinoma (OSCC) cell phenotype. Additionally, we also investigated a theoretical consequence of Metformin treatment. METHODS: PDH levels in patients with OSCC and oral dysplasia were evaluated. Metformin was administered in vitro to test the effect of Metformin under hypoxic conditions. The results were complemented by Bioinformatics analyses. CONCLUSIONS: In conclusion, our current findings show that Metformin reduces HIF-1α gene expression and increases PDH expression. Metformin inhibits cell proliferation and migration in the OSCC cell line model. Additionally, Metformin enhances the number of apoptotic cells and caspase 3 levels. Interestingly enough, Metformin did not increase the mutant p53 levels under hypoxic conditions.


Subject(s)
Carcinoma, Squamous Cell/genetics , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Metformin/pharmacology , Mouth Neoplasms/genetics , Pyruvate Dehydrogenase Complex/genetics , Apoptosis/drug effects , Apoptosis/genetics , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/pathology , Cell Death/drug effects , Cell Death/genetics , Cell Hypoxia , Cell Line , Cell Line, Tumor , Cell Movement/drug effects , Cell Movement/genetics , Cell Proliferation/drug effects , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic/drug effects , Humans , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Mouth Neoplasms/metabolism , Mouth Neoplasms/pathology , Pyruvate Dehydrogenase Complex/metabolism , Signal Transduction/drug effects , Signal Transduction/genetics
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