Enhancement by Nano-Diamino-Tetrac of Antiproliferative Action of Gefitinib on Colorectal Cancer Cells: Mediation by EGFR Sialylation and PI3K Activation

Tung Cheng Chang, Yu Tang Chin, André Wendindondé Nana, Shwu Huey Wang, Yu Min Liao, Yi Ru Chen, Ya Jung Shih, Chun A. Changou, Yu Chen Sh Yang, Kuan Wang, Jacqueline Whang-Peng, Liang Shun Wang, Steven C. Stain, Ai Shih, Hung Yun Lin, Chih Hsiung Wu, Paul J. Davis

研究成果: 雜誌貢獻文章

8 引文 斯高帕斯(Scopus)

摘要

Drug resistance complicates the clinical use of gefitinib. Tetraiodothyroacetic acid (tetrac) and nano-diamino-tetrac (NDAT) have been shown in vitro and in xenografts to have antiproliferative/angiogenic properties and to potentiate antiproliferative activity of other anticancer agents. In the current study, we investigated the effects of NDAT on the anticancer activities of gefitinib in human colorectal cancer cells. β-Galactoside α-2,6-sialyltransferase 1 (ST6Gal1) catalyzes EGFR sialylation that is associated with gefitinib resistance in colorectal cancers, and this was also investigated. Gefitinib inhibited cell proliferation of HT-29 cells (K-ras wild-type), and NDAT significantly enhanced the antiproliferative action of gefitinib. Gefitinib inhibited cell proliferation of HCT116 cells (K-ras mutant) only in high concentration, and this was further enhanced by NDAT. NDAT enhancedd gefitinib-induced antiproliferation in gefitinib-resistant colorectal cancer cells by inhibiting ST6Gal1 activity and PI3K activation. Furthermore, NDAT enhanced gefitinib-induced anticancer activity additively in colorectal cancer HCT116 cell xenograft-bearing nude mice. Results suggest that NDAT may have an application with gefitinib as combination colorectal cancer therapy.
原文英語
頁(從 - 到)420-432
頁數13
期刊Hormones and Cancer
9
發行號6
DOIs
出版狀態已發佈 - 十二月 1 2018

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Oncology
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Cancer Research

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