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. 2020 Jul-Sep;61(3):707-714.
doi: 10.47162/RJME.61.3.09.

Adjuvant effects of chemotherapeutics and Metformin on MFE-319 endometrial carcinoma cell line

Isil Aydemir  1 , Elgin Turkoz Uluer, Oya Korkmaz, Mehmet Ibrahim Tuglu, Sevinc Inan
Affiliations

Adjuvant effects of chemotherapeutics and Metformin on MFE-319 endometrial carcinoma cell line

Isil Aydemir et al. Rom J Morphol Embryol. 2020 Jul-Sep.

Abstract

We aimed to investigate the cytotoxicity of Metformin, Cisplatin, and Paclitaxel on MFE-319 endometrial carcinoma cell line using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and immunocytochemistry assays. Half maximal inhibitory concentration (IC50) doses of three drugs alone and in the dual combinations were applied to the cells. Immunocytochemical method was performed for the cell survival and for phosphatidylinositol 3-kinase (PI3K), phosphorylated extracellular regulated kinases (pErk)-1∕2, Akt-1, phosphorylated Akt (pAkt)-1∕2∕3 cell growth markers and angiogenic vascular endothelial growth factor (VEGF). Immunoreactivities were evaluated using H-score and analyzed using the one-way analysis of variance (ANOVA) test for statistics. It was found that these drugs caused a decrease in the immunoreactivities of these markers. Particularly, dual combination of Paclitaxel and Cisplatin decreased the immunoreactivities of PI3K, pErk-1∕2, Akt-1, and pAkt-1∕2∕3. Cisplatin and Paclitaxel were more effective than Metformin; on the other hand, Metformin has been shown to enhance the efficacy of these two drugs. In vitro or in vivo further studies are needed to investigate the efficacy of these three drugs via PI3K∕Akt signal pathway.

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Conflict of interest statement

The authors declare no conflict of interests.

Figures

Figure 1
Figure 1
The survival of MFE-319 endometrial carcinoma cells with Metformin (A), Paclitaxel (B) and Cisplatin (C) for 24 hours was analyzed using MTT assay. Percentage of cell survival was analyzed using the one-way ANOVA test with Tukey–Kramer multiple comparisons test. ANOVA: Analysis of variance; MTT: 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; SD: Standard deviation
Figure 2
Figure 2
The H-score analysis of immunocytochemical staining of Akt-1, pAkt-1/2/3, pErk-1/2, PI3K and VEGF in MFE-319 endometrial carcinoma cells after application with Paclitaxel, Cisplatin and Metformin for 24 hours. pAkt-1/2/3: Phosphorylated Akt-1/2/3; pErk-1/2: Phosphorylated extracellular regulated kinases-1/2; PI3K: Phosphatidyl-inositol 3-kinase; SD: Standard deviation; VEGF: Vascular endothelial growth factor
Figure 3
Figure 3
The immunocytochemical staining of Akt-1, pAkt-1/2/3, pErk-1/2, PI3K and VEGF in MFE-319 endometrial carcinoma cells after application with Paclitaxel (Pac), Cisplatin (Cisp), Metformin (Met), and dual combinations of drugs for 24 hours. Arrows: Immunopositive cells. Scale bars: 10 μm. pAkt-1/2/3: Phosphorylated Akt-1/2/3; pErk-1/2: Phosphorylated extracellular regulated kinases-1/2; PI3K: Phosphatidylinositol 3-kinase; VEGF: Vascular endothelial growth factor
Figure 4
Figure 4
The H-score analysis of immunocytochemical staining of Akt-1, pAkt-1/2/3, pErk-1/2, PI3K and VEGF in MFE-319 endometrial carcinoma cells after application with the dual combinations of Paclitaxel (Pac), Cisplatin (Cisp) and Metformin (Met) for 24 hours. pAkt-1/2/3: Phosphorylated Akt-1/2/3; pErk-1/2: Phosphorylated extracellular regulated kinases-1/2; PI3K: Phosphatidylinositol 3-kinase; SD: Standard deviation; VEGF: Vascular endothelial growth factor
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