Galectin-3 regulates apoptosis and doxorubicin chemoresistance in papillary thyroid cancer cells.
A subset of patients with papillary thyroid cancer (PTC) present with aggressive disease that is refractory to conventional treatment. Novel therapies are needed to treat this group of patients. Galectin-3 (Gal-3) is a beta-galactoside-binding protein with anti-apoptotic activity. Over 30 studies in the last 3 years have reported that Gal-3 is highly expressed in PTC relative to normal thyrocytes. In this study, we show that Gal-3 silencing with RNA interference stimulates apoptosis, while Gal-3 overexpression protects against both TRAIL- and doxorubicin-induced apoptosis in PTC cells. The anti-apoptotic activity and chemoresistance related to Gal-3 function can be partially reversed through the inhibition of the PI3K-Akt pathway, suggesting that Gal-3 acts, at least in part, on the PI3K-Akt axis. These observations support further evaluation of Gal-3 as a potential therapeutic target in patients with aggressive PTC.
Lin
Chi-Iou
CI
Department of Surgery, Brigham and Women's Hospital, 20 Shattuck St., Thorn 1503, Boston, MA 02115, USA.
Whang
Edward E
EE
Abramson
Michael A
MA
Donner
David B
DB
Bertagnolli
Monica M
MM
Moore
Francis D
FD
Ruan
Daniel T
DT
D000231:Adenocarcinoma, Papillary / Q000378:metabolism* / Q000473:pathology; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000235:genetics*; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D037502:Galectin 3 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology; D013964:Thyroid Neoplasms / Q000378:metabolism* / Q000473:pathology
D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin; D037502:Galectin 3; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D034741:RNA, Small Interfering; D053221:TNF-Related Apoptosis-Inducing Ligand