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Galectin-3 Targeted...
Galectin-3 Targeted Therapy with a Small Molecule Inhibitor Activates Apoptosis and Enhances Both Chemosensitivity and Radiosensitivity in Papillary Thyroid Cancer
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Lin, Chi-lou (author)
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Whang, Edward E. (author)
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Donner, David B. (author)
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Jiang, Xiaofeng (author)
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Price, Brendan D. (author)
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Carothers, Adelaide M. (author)
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Delaine, Tamara (author)
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- Leffler, Hakon (author)
- Lund University,Lunds universitet,Avdelningen för mikrobiologi, immunologi och glykobiologi - MIG,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Microbiology, Immunology and Glycobiology - MIG,Department of Laboratory Medicine,Faculty of Medicine
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- Nilsson, Ulf (author)
- Lund University,Lunds universitet,Centrum för analys och syntes,Kemiska institutionen,Institutioner vid LTH,Lunds Tekniska Högskola,Centre for Analysis and Synthesis,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH
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Nose, Vania (author)
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Moore, Francis D., Jr. (author)
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Ruan, Daniel T. (author)
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(creator_code:org_t)
- 2009
- 2009
- English.
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In: Molecular Cancer Research. - 1557-3125. ; 7:10, s. 1655-1662
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
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- Although most patients with papillary thyroid cancer (PTC) have favorable outcomes, some have advanced PTC that is refractory to external beam radiation and systemic chemotherapy. Galectin-3 (Gal-3) is a beta-galactoside-binding protein with antiapoptotic activity that is consistently overexpressed in PTC. The purpose of this study is to determine if Gal-3 inhibition promotes apoptosis, chemosensitivity, and radiosensitivity in PTC. PTC cell lines (8505-C and TPC-1) and human ex vivo PTC were treated with a highly specific small molecule inhibitor of Gal-3 (Td131_1). Apoptotic activity was determined by flow cytometric analysis as well as caspase-3 and PARP cleavage. The minimum inhibitory concentrations of Td131_1 and doxorubicin were determined, and their combined effects were measured to test for synergistic activity. The effects of Td131_1 on radiosensitivity were determined by a clonogenic assay. Td131_1 promoted apoptosis, improved radiosensitivity, and synergistically enhanced chemosensitivity to doxorubicin in PTC cell lines. In PTC ex vivo, Td131_1 treatment alone induced the cleavage of caspase-3 and PARP. Td131_1 and doxorubicin together activated apoptosis in PTC ex vivo to a greater degree than their combined individual effects. Td131_1 activated apoptosis and had synergistic activity with doxorubicin in PTC. We conclude that Gal-3 targeted therapy is a promising therapeutic strategy for advanced PTC that is refractory to surgery and radioactive iodine therapy. (Mol Cancer Res 2009;7(10):1655-62)
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
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- art (subject category)
- ref (subject category)
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- By the author/editor
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Lin, Chi-lou
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Whang, Edward E.
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Donner, David B.
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Jiang, Xiaofeng
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Price, Brendan D ...
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Carothers, Adela ...
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show more...
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Delaine, Tamara
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Leffler, Hakon
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Nilsson, Ulf
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Nose, Vania
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Moore, Francis D ...
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Ruan, Daniel T.
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
- Articles in the publication
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Molecular Cancer ...
- By the university
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Lund University