Table 2.
The table summarizes the effects of metformin on different endocrine tumors as reported in various preclinical studies.
| Endocrine tumors | Reference | Study design (cell lines) | Metformin dose | Study endpoint |
|---|---|---|---|---|
| Thyroid cancer | (Klubo-Gwiezdzinska et al. 2013) | In-vitro study (FTC133, TPC1, BCPAP) | Variable (0.5–5 mM) | Dose- and time-dependent reduction in cellular proliferation in DTC cells |
| Thyroid cancer | (Chen, et al. 2012) | In-vitro study (HTh74, HTh74Rdox, C643, SW1736, FTC133) | Variable (0.1–40 mM) | Metformin treatment inhibited cell proliferation, cell cycle progression and promoted apoptosis in thyroid cancer cells in a dose-dependent manner |
| PTC | (Cho, et al. 2014) | In-vitro study (BCPAP, BHP10–3SC) | Variable (0.1–20 mM) | Dose-dependent inhibition of cellular viability and induction of apoptosis in PTC cells |
| In-vivo study (BHP10–3SC) | Variable (10, 50, 100 mg/ml of metformin in drinking water for 30 days) | Dose-dependent reduction in tumor volume in PTC mouse model | ||
| DTC | (Thakur, et al. 2018) | In-vitro study (FTC133, BCPAP) | 5 mM | Inhibition of cellular proliferation as well as mitochondrial respiration in DTC cells |
| In-vivo study (FTC133) | 12.5 mg in water by oral gavage for 4 weeks | Inhibition of tumor growth in a DTC mouse model characterized by high mGPDH expression | ||
| PTC | (Shen, et al. 2017) | In-vitro study (BCPAP, KTC1) | Variable (2.5– 10 mM) | Reduction in cellular viability and glucose uptake |
| In-vivo study (BCPAP) | 300 mg/kg/day by intraperitoneal injections for a week | Reduction in glucose uptake | ||
| Thyroid cancer | (Kheder, et al. 2017) | In-vitro study (FTC133, K1E7, RO82-W-1, 8305C, TT, Nthy-ori 3–1) | Variable (0.03–20 mM) | Inhibition of cellular proliferation, migration and induction of apoptosis in a variety of thyroid cancer cell lines in a dose-dependent manner |
| Obesity-induced thyroid cancer | (Park, et al. 2016) | In-vivo study (ThrbPV/PVPten+/-mice) | 0.5 mg/ml in drinking water | Inhibition of tumor progression by blocking vascular invasion and anaplasia in obesity-induced thyroid cancer mice models |
| Obesity-induced thyroid cancer | (Park, et al. 2018) | In-vivo study (ThrbPV/PVPten+/- mice) | 0.5 mg/ml in drinking water | Metformin, in combination with JQ1, led to a reduction in thyroid cancer growth and improved survival in obesity-induced thyroid cancer mice models |
| MTC | (Klubo-Gwiezdzinska, et al. 2012) | In-vitro study (TT and MZ-CRC-1) | Variable (0.5–5 mM) | Inhibition of cellular growth in a dose- and time-dependent manner |
| ATC | (Nozhat et al. 2018) | In-vitro study (SW1736, C643, 8305C) | Variable (2.5–60 mM) | Dose-dependent reduction in cellular viability, migration and induction of apoptosis |
| ATC | (Chen, et al. 2015) | In-vitro study (HTh7, HTh74Rdox) | 5 mM | Metformin, in combination with sorafenib, resulted in increased apoptosis and cell cycle arrest |
| ATC | (Hanly, et al. 2015) | In-vitro study (Nthy-ori 3, BCPAP, 8505c) | 2 mM | Metformin, in combination with vemurafenib, resulted in increased loss of cellular viability and induction of apoptosis |
| NET | (Vlotides, et al. 2014) | In-vitro study (BON1, GOT1, NCI-H727) | Variable (0.1–10 mM) | Dose and time-dependent decrease in cell viability |
| pNET | (Herrera-Martinez, et al. 2019) | In-vitro study (BON1, QGP-1) | 10mM | Time-dependent decrease in cell viability |
| PCC | (Li, et al. 2017) | In-vitro study (PC12) | Variable (1–50 mM) | Dose-dependent reduction in cellular viability, inhibition of cell cycle progression and promotion of cell apoptosis |
| PGL | (Florio, et al. 2018) | In-vitro study (PTJ64i and PTJ86i) | Variable (5–40 mM) | Dose-dependent inhibition of cellular viability |
| ACC | (Poli, et al. 2016) | In-vitro study (H295R, SW13) | Variable (0.5– 250 mM) | Dose-dependent reduction in cellular viability, proliferation and induction of apoptosis |
| In-vivo study (H295R) | 3 mg/100 µL PBS for 40 days | Reduction in tumor volume | ||
| PitNETs | (An, et al. 2017) | In-vitro study (GH3) | Variable (2–50 mM) | Dose-dependent reduction in cellular proliferation, growth hormone secretion, and induction of apoptosis |
| In-vivo study (GH3) | Variable (100, 300, 500 mg/kg for 4 weeks) | Dose-dependent reduction in tumor size and growth hormone secretion | ||
| PitNETs | (Faggi, et al. 2018) | In-vitro study (GH3) | Variable (0.4– 5 mM) | Inhibition of cellular viability |
| PitNETs | (Vazquez-Borrego, et al. 2019) | In-vitro study (Primary culture on ACTH-secreting adenomas, non-functioning pituitary adenomas, GH-secreting adenomas, prolactinomas; cell lines- AtT20, GH3) | 5mM, 10mM | Inhibition of cellular viability in a cell type dependent manner. |
| Pituitary corticotroph tumor | (Jin, et al. 2018) | In-vitro study (AtT20) | Variable (2.5–40 mM) | Reduction in cellular proliferation, ACTH secretion and induction of apoptosis |