Effects of insulin analogs and glucagon-like peptide-1 receptor agonists on proliferation and cellular energy metabolism in papillary thyroid cancer

Figures & data

Figure 1 Expressions of IR, IGF-1R, and GLP-1R in human thyroid tissues and cells.

Notes: (A) IR, IGF-1R, and GLP-1R IHC (×200) of PTC and normal tissues. (B) Expression of IR, IGF-1R, and GLP-1R in primary cultured thyrocytes and PTC cell lines. Scale bar =100 μm.
Abbreviations: GLP-1R, glucagon-like peptide-1 receptor; IGF-1R, insulin-like growth factor receptor; IHC, immunohistochemistry; IR, insulin receptor; PTC, papillary thyroid cancer.

Figure 2 Effects of regular insulin and insulin analogs on the proliferation of PTC cell lines.

Notes: Results from MTT assays at 48 h after the treatment. (A) IHH4, (B) BCPAP, and (C) TPC-1.
Abbreviations: BCPAP, normal human thyroid cells; IHH4, human papillary thyroid carcinoma cell line; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; PTC, papillary thyroid cancer; TPC-1, human thyroid cancer cell line.

Figure 3 Effects of regular insulin and insulin analogs on PI3K/Akt and MAPK/Erk signaling pathways in PTC cell lines.

Notes: PTC cells were treated with insulin or each insulin analog at 1,500 nmol/L for 48 h. (A) IHH4, (B) BCPAP, and (C) TPC-1.
Abbreviations: Akt, AKT serine/threonine kinase; BCPAP, normal human thyroid cells; Erk, extracellular signal-regulated kinase; IHH4, human papillary thyroid carcinoma cell line; MAPK, mitogen-activated protein kinase; PI3K, phosphoinositol-3 kinase; PTC, papillary thyroid cancer; TPC-1, human thyroid cancer cell line.

Figure 4 Effects of regular insulin and insulin analogs on mitochondrial respiration and glycolysis in PTC cell lines.

Notes: PTC cells were treated with insulin or each insulin analog at 1,500 nmol/L for 48 h. Oligomycin (1 μM), FCCP (0.25 μM), rotenone (1 μM), and antimycin A (1 μM) were delivered at indicated times to determine different parameters of mitochondrial functions; glucose (10 mM), oligomycin (1.0 μM), and 2-deoxy-D-glucose (100 mM) were delivered at indicated times to determine different parameters of glycolysis status. These drugs were added according to the manufacturer’s protocols. (A) IHH4, (B) BCPAP, and (C) TPC-1.
Abbreviations: BCPAP, normal human thyroid cells; ECAR, extracellular acidification rate; FCCP, p-trifluoromethoxyphenylhydrazone; IHH4, human papillary thyroid carcinoma cell line; OCR, oxygen consumption rate; PTC, papillary thyroid cancer; TPC-1, human thyroid cancer cell line.

Figure 5 Effects of GLP-1R agonists on the proliferation of PTC cell lines.

Notes: Results from MTT assays at 24, 48, and 72 h after the treatment. (A) IHH4, (B) BCPAP, and (C) TPC-1.
Abbreviations: BCPAP, normal human thyroid cells; GLP-1R, glucagon-like peptide-1 receptor; IHH4, human papillary thyroid carcinoma cell line; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; PTC, papillary thyroid cancer; TPC-1, human thyroid cancer cell line.

Figure 6 Effects of GLP-1R agonists on PI3K/Akt and MAPK/Erk signaling pathways in PTC cell lines.

Notes: PTC cells were treated with liraglutide or exenatide (100 nmol/L) for 48 h. (A) IHH4, (B) BCPAP, and (C) TPC-1.
Abbreviations: Akt, AKT serine/threonine kinase; BCPAP, normal human thyroid cells; Erk, extracellular signal-regulated kinase; GLP-1R, glucagon-like peptide-1 receptor; IHH4, human papillary thyroid carcinoma cell line; MAPK, mitogen-activated protein kinase; PI3K, phosphoinositol-3 kinase; PTC, papillary thyroid cancer; TPC-1, human thyroid cancer cell line.

Figure 7 Effects of GLP-1R agonists on mitochondrial respiration and glycolysis in PTC cell lines.

Notes: PTC cells were treated with liraglutide or exenatide (100 nmol/L) for 48 h. Oligomycin (1 μM), FCCP (0.25 μM), rotenone (1 μM), and antimycin A (1 μM) were delivered at the indicated times to determine different parameters of mitochondrial functions; glucose (10 mM), oligomycin (1.0 μM), and 2-deoxy-D-glucose (100 mM) were delivered at indicated times to determine different parameters of glycolysis status. These drugs were added according to the manufacturer’s protocols. (A) IHH4, (B) BCPAP, and (C) TPC-1.
Abbreviations: BCPAP, normal human thyroid cells; ECAR, extracellular acidification rate; FCCP, p-trifluoromethoxyphenylhydrazone; GLP-1R, glucagon-like peptide-1 receptor; IHH4, human papillary thyroid carcinoma cell line; OCR, oxygen consumption rate; PTC, papillary thyroid cancer; TPC-1, human thyroid cancer cell line.