@article{afc30808e8c247a3ba91e2bc3b061e89,
title = "Enhancement by Nano-Diamino-Tetrac of Antiproliferative Action of Gefitinib on Colorectal Cancer Cells: Mediation by EGFR Sialylation and PI3K Activation",
abstract = "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.",
author = "Chang, {Tung Cheng} and Chin, {Yu Tang} and Nana, {Andr{\'e} Wendindond{\'e}} and Wang, {Shwu Huey} and Liao, {Yu Min} and Chen, {Yi Ru} and Shih, {Ya Jung} and Changou, {Chun A.} and Yang, {Yu Chen Sh} and Kuan Wang and Jacqueline Whang-Peng and Wang, {Liang Shun} and Stain, {Steven C.} and Ai Shih and Lin, {Hung Yun} and Wu, {Chih Hsiung} and Davis, {Paul J.}",
note = "Funding Information: Acknowledgments This work was supported in part by a grant from Shuang-Ho Hospital Collaborating Program (T.C. Chang, 103TMU-SHH-20), by Chair Professor Research Fund to Dr. J. Whang-Peng, by Chair Professor Research Fund to Dr. K. Wang, grant from Ministry of Education (TMUTOP103006-4, The Aim for the Top University Project-Cancer Translational Center of Taipei Medical University, funding to excellent character program, Taipei Medical University), the “TMU Research Center of Cancer Translational Medicine” from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE) in TaiwanGeneral grants of Ministry of Science and Technology Taiwan (H.Y. Lin, MOST104-2320-B-038-009; MOST105-2320-B-038-006; MOST104-2314-B-038-046-MY3). Funding Information: This work was supported in part by a grant from Shuang-Ho Hospital Collaborating Program (T.C. Chang, 103TMU-SHH-20), grant from Ministry of Education (TMUTOP103006-4, The Aim for the Top University Project- Cancer Translational Center of Taipei Medical University, funding to excellent character program, Taipei Medical University), the “TMU Research Center of Cancer Translational Medicine” from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE) in TaiwanGeneral grants of Ministry of Science and Technology Taiwan (H.Y. Lin, MOST104-2320-B-038-009; MOST105-2320-B-038-006; MOST104-2314-B-038-046-MY3). Co-author PJD is a co-inventor of NDAT and a stockholders in a company that is commercializing the agent. Other co-authors declare no competing financial interests. Publisher Copyright: {\textcopyright} 2018, The Author(s).",
year = "2018",
month = dec,
day = "1",
doi = "10.1007/s12672-018-0341-x",
language = "English",
volume = "9",
pages = "420--432",
journal = "Hormones and Cancer",
issn = "1868-8497",
publisher = "Springer US",
number = "6",
}
