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Galectin-3 Targeted Therapy with a Small Molecule Inhibitor Activates Apoptosis and Enhances Both Chemosensitivity and Radiosensitivity in Papillary Thyroid Cancer

Författare

  • Chi-lou Lin
  • Edward E. Whang
  • David B. Donner
  • Xiaofeng Jiang
  • Brendan D. Price
  • Adelaide M. Carothers
  • Tamara Delaine
  • Hakon Leffler
  • Ulf Nilsson
  • Vania Nose
  • Francis D., Jr. Moore
  • Daniel T. Ruan

Summary, in English

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)

Publiceringsår

2009

Språk

Engelska

Sidor

1655-1662

Publikation/Tidskrift/Serie

Molecular Cancer Research

Volym

7

Issue

10

Dokumenttyp

Artikel i tidskrift

Förlag

American Association for Cancer Research

Ämne

  • Cancer and Oncology

Status

Published

ISBN/ISSN/Övrigt

  • ISSN: 1557-3125