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Endocrine

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28.12.2017 | Original Article

Synergistic cytotoxicity of the dipeptidyl peptidase-IV inhibitor gemigliptin with metformin in thyroid carcinoma cells

verfasst von: Si Hyoung Kim, Jun Goo Kang, Chul Sik Kim, Sung-Hee Ihm, Moon Gi Choi, Hyung Joon Yoo, Seong Jin Lee

Erschienen in: Endocrine | Ausgabe 2/2018

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Abstract

Purpose

The influence of the dipeptidyl peptidase-IV inhibitor, gemigliptin alone or in combination with metformin on survival, proliferation, and migration of thyroid carcinoma cells was investigated.

Methods

SW1736 and TPC-1 human thyroid carcinoma cells were used.

Results

Gemigliptin and metformin caused cell death in a dose-dependent manner. In cells treated with both gemigliptin and metformin, compared with metformin alone, all of the combination index values were lower than 1.0, suggesting synergistic cytotoxicity of two agents. Cell viability, the percentage of viable cells, ATP levels, and mitochondrial membrane potential decreased; however, cytotoxic activity, and the protein levels of cleaved PARP, phospho-Akt and phospho-AMP-activated protein kinase (AMPK) increased. Administration of wortmannin, but not compound C, further decreased cell viability, and further increased cytotoxic activity. Moreover, compared with control, cell proliferation and migration as well as the protein levels of p53, p21, vascular cell adhesion molecule-1 (VCAM-1), and phospho-extracellular signal-regulated kinase (ERK) 1/2 decreased. The decrement of matrix metalloproteinase-2 and matrix metalloproteinase-9 protein levels was cell specific.

Conclusions

Our results demonstrate that gemigliptin induces cytotoxic activity, and has a synergistic activity with metformin in inducing cytotoxicity via regulation of Akt and AMPK in thyroid carcinoma cells. Furthermore, gemigliptin augments the inhibitory effect of metformin on proliferation and migration through involvement of matrix metalloproteinase-2, matrix metalloproteinase-9, p53, p21, VCAM-1, and ERK in thyroid carcinoma cells.

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Titel: Synergistic cytotoxicity of the dipeptidyl peptidase-IV inhibitor gemigliptin with metformin in thyroid carcinoma cells
verfasst von: Si Hyoung Kim
Jun Goo Kang
Chul Sik Kim
Sung-Hee Ihm
Moon Gi Choi
Hyung Joon Yoo
Seong Jin Lee
Publikationsdatum: 28.12.2017
Verlag: Springer US
Erschienen in: Endocrine / Ausgabe 2/2018
Print ISSN: 1355-008X
Elektronische ISSN: 1559-0100
DOI: https://doi.org/10.1007/s12020-017-1503-2

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Synergistic cytotoxicity of the dipeptidyl peptidase-IV inhibitor gemigliptin with metformin in thyroid carcinoma cells

Abstract

Purpose

Methods

Results

Conclusions

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Parodontalbehandlung verbessert Prognose bei Katheterablation

Antihypertensiva schützen auch alte Menschen noch vor Demenz

Stereotaktische Radiatio schlägt konventionelle Bestrahlung

Denken Sie bei starker Blutung auch an die Hemmkörper-Hämophilie

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Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

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Abstract

Purpose

Methods

Results

Conclusions

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