Rosiglitazone Inhibits Adrenocortical Cancer Cell Proliferation by Interfering with the IGF-IR Intracellular Signaling
Giulia Cantini,
Adriana Lombardi,
Elisabetta Piscitelli,
Giada Poli,
Elisabetta Ceni,
Sara Marchiani,
Tonino Ercolino,
Andrea Galli,
Mario Serio,
Massimo Mannelli,
Michaela Luconi
Affiliations
Giulia Cantini
DENOthe Center of Excellence for Research, Transfer and High Education: Section of Endocrinology, Department of Clinical Physiopathology, University of Florence, Viale Pieraccini 6, 50139 Firenze, Italy
Adriana Lombardi
DENOthe Center of Excellence for Research, Transfer and High Education: Section of Endocrinology, Department of Clinical Physiopathology, University of Florence, Viale Pieraccini 6, 50139 Firenze, Italy
Elisabetta Piscitelli
DENOthe Center of Excellence for Research, Transfer and High Education: Section of Endocrinology, Department of Clinical Physiopathology, University of Florence, Viale Pieraccini 6, 50139 Firenze, Italy
Giada Poli
DENOthe Center of Excellence for Research, Transfer and High Education: Section of Endocrinology, Department of Clinical Physiopathology, University of Florence, Viale Pieraccini 6, 50139 Firenze, Italy
Elisabetta Ceni
DENOthe Center of Excellence for Research, Transfer and High Education: Section of Gastroenterology, Department of Clinical Physiopathology, University of Florence, Viale Pieraccini 6, 50139 Firenze, Italy
Sara Marchiani
DENOthe Center of Excellence for Research, Transfer and High Education: Section of Andrology, Department of Clinical Physiopathology, University of Florence, Viale Pieraccini 6, 50139 Firenze, Italy
Tonino Ercolino
DENOthe Center of Excellence for Research, Transfer and High Education: Section of Endocrinology, Department of Clinical Physiopathology, University of Florence, Viale Pieraccini 6, 50139 Firenze, Italy
Andrea Galli
DENOthe Center of Excellence for Research, Transfer and High Education: Section of Gastroenterology, Department of Clinical Physiopathology, University of Florence, Viale Pieraccini 6, 50139 Firenze, Italy
Mario Serio
DENOthe Center of Excellence for Research, Transfer and High Education: Section of Endocrinology, Department of Clinical Physiopathology, University of Florence, Viale Pieraccini 6, 50139 Firenze, Italy
Massimo Mannelli
DENOthe Center of Excellence for Research, Transfer and High Education: Section of Endocrinology, Department of Clinical Physiopathology, University of Florence, Viale Pieraccini 6, 50139 Firenze, Italy
Michaela Luconi
DENOthe Center of Excellence for Research, Transfer and High Education: Section of Endocrinology, Department of Clinical Physiopathology, University of Florence, Viale Pieraccini 6, 50139 Firenze, Italy
Rosiglitazone (RGZ), a thiazolidinedione ligand of the peroxisome proliferator-activated receptor (PPAR)-γ, has been recently described as possessing antitumoral properties. We investigated RGZ effect on cell proliferation in two cell line models (SW13 and H295R) of human adrenocortical carcinoma (ACC) and its interaction with the signaling pathways of the activated IGF-I receptor (IGF-IR). We demonstrate a high expression of IGF-IR in the two cell lines and in ACC. Cell proliferation is stimulated by IGF-I in a dose- and time-dependent manner and is inhibited by RGZ. The analysis of the main intracellular signaling pathways downstream of the activated IGF-IR, phosphatidyl inositol 3-kinase (PI3K)-Akt, and extracellular signal-regulated kinase (ERK1/2) cascades reveals that RGZ rapidly interferes with the Akt and ERK1/2 phosphorylation/activation which mediates IGF-I stimulated proliferation. In conclusion, our results suggest that RGZ exerts an inhibitory effect on human ACC cell proliferation by interfering with the PI3K/Akt and ERK1/2 signaling pathways downstream of the activated IGF-IR.
