. 2022 Mar 21;13(6):1859-1870.
doi: 10.7150/jca.63234.
eCollection 2022.
Affiliations
Item in Clipboard
J Cancer.
.
Abstract
Objectives: Metformin, a first-line drug that has been used for type 2 diabetes treatment, recently attracts broad attention for its therapeutic effects on diverse human cancers. However, its effect and the underlying mechanisms on oral squamous cell carcinoma (OSCC) are not well known. Materials and Methods: OSCC cells were used to evaluate the effect of metformin on cell proliferation and colony formation in vitro. Tumor formation assay in nude mice was conducted to assess the effect of metformin in vivo. Western blotting and immunohistochemistry stain were performed to investigate the effect of metformin on the expression of acetylation at lysine 27 of histone H3 (H3K27ac) and methylation at lysine 27 of histone H3 (H3K27me3) in vitro and in vivo. RNA-seq and ChIP-seq were performed to explore the genome profile to metformin treatment in OSCC cells. Results: Metformin inhibited OSCC cell proliferation and colony formation in vitro, as well as OSCC growth in vivo. Metformin increased the global H3K27ac modification in vitro. Transcriptome analysis suggested that metformin mainly downregulated pluripotency stem cell pathway, development involved pathways and upregulated cytokine and inflammatory pathways. Additionally, H3K27ac was involved in transcription, DNA repair and replication in metformin-treated OSCC cells. Conclusions: Metformin inhibits OSCC growth concomitant upregulated global level of H3K27ac in vitro. This study provides insights into the molecule and epigenome basis on application of metformin in OSCC treatment, and highlights the underlying mechanisms of reprogrammed cancer regulation and epigenetic histone modification.
Keywords:
H3K27ac; H3K27me3; Metformin; oral squamous cell carcinoma; reprogrammed cancer regulation.
© The author(s).
Conflict of interest statement
Competing Interests: The authors have declared that no competing interest exists.
Figures
References
-
-
Peres MA, Macpherson LMD, Weyant RJ, Daly B, Venturelli R, Mathur MR. et al. Oral diseases: a global public health challenge. Lancet (London, England) 2019;394:249–60.
–
PubMed
-
-
-
D’Cruz AK, Vaish R, Dhar H. Oral cancers: Current status. Oral oncology. 2018;87:64–9.
–
PubMed
-
-
-
Chan KK, Glenny AM, Weldon JC, Furness S, Worthington HV, Wakeford H. Interventions for the treatment of oral and oropharyngeal cancers: targeted therapy and immunotherapy. The Cochrane database of systematic reviews. 2015: Cd010341.
–
PubMed
-
-
-
Hartner L. Chemotherapy for Oral Cancer. Dental clinics of North America. 2018;62:87–97.
–
PubMed
-
Read more here: Source link