The Effect of Metformin on SIK1 and SIK2 in MCF-7 Cell as an Anticancer Agent

Recent studies have shown that the use of metformin prevents the development and spread of cancer. Metformin may show this effect by increasing SIK1 and SIK2 gene expression. For this purpose, MCF-7 cells cultured in appropriate media were divided into 8 groups (1) control, (2) 10 ng/mL TGF- β 1, (3) 1.25 mM Metformin, (4) 2.5mM Metformin, (5) 20mM Metformin, (6) 1.25 mM Metform-in+10 ng/ml TGF- β 1, (7) 2.5mM Metformin+10 ng/ml TGF- β 1 and (8) 20mM Metformin+10 ng/ml TGF- β 1 doses were administered, respectively. PCR was performed for SIK1 and SIK2 genes, with GAPDH being the reference gene. Application of 10 ng/ml TGF- β 1 to MCF-7 cell significantly increased expression level of SIK1 mRNA by 1.6 fold. In non-invasive (TGF- β 1 not administered) MCF-7 cell, 2.5 mM and 20 mM metformin increased expression levels of SIK1 mRNA by 1.8, 3.4 fold and SIK2 mRNA by 1.6 and 3.3 fold respectively. In invasive (TGF- β 1 administered) MCF-7 cell, 1.25, 2.5 and 20 mM metformin increased expression levels of SIK1 mRNA by 3.5, 3.7, 4 fold; and SIK2 mRNA by 1.9, 2.4, 3.5 fold, respectively. Metformin increased SIK1 and SIK2 gene expression dose-dependently in non-invasive and invasive MCF-7 cells, more significantly in invasive ones. The increase in the SIK1 gene was greater than in SIK2. In the light of these results, investigating the effects of metformin on SIK1 and SIK2 genes in different TGF- β 1 sensitive cancer types may open new doors for cancer treatment.