Abstract

Colorectal cancer is a serious medical problem in Taiwan. New, effective therapeutic approaches are needed. The selection of promising anticancer drugs and the transition from pre-clinical investigations to clinical trials are often challenging. The deaminated thyroid hormone analog (tetraiodothyroacetic acid, tetrac) and its nanoparticulate analog (NDAT) have been shown to have anti-proliferative activity in vitro and in xenograft model of different neoplasms, including colorectal cancers. However, mechanisms involved in tetrac- and NDAT-induced antiproliferation in colorectal cancers are incompletely understood. We have investigated possible mechanisms of tetrac and NDAT action in colorectal cancer cells, using a perfusion bellows cell culture system that allows efficient, large-scale screening for mechanisms of drug actions on tumor cells. Although integrin αvβ3 in K-RAS wild type colorectal cancer HT-29 cells was far less than that in K-RAS mutant HCT116 cells, HT-29 was more sensitive to both tetrac and NDAT. Results also indicate that both tetrac and NDAT bind to tumor cell surface integrin αvβ3, and the agents may have different mechanisms of antiproliferation in colorectal cancer cells. K-RAS status appears to play an important role in drug resistance that may be encountered in treatment with this drug combination.

Original languageEnglish
Article number130
Pages (from-to)130
JournalFrontiers in Endocrinology
Volume10
Issue numberAPR
DOIs
Publication statusPublished - Jan 1 2019

Keywords

  • Anticancer
  • Colorectal cancer cells
  • Integrin αvβ3
  • NDAT
  • Perfusion bellows cell culture system
  • PhosphoERK1/2
  • Tetrac

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism

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  • Cite this

    Chin, Y-T., He, Z-R., Chen, C-L., Chu, H-C., Ho, Y., Su, P-Y., Yang, Y-C. S. H., Wang, K., Shih, Y-J., Chen, Y-R., Pedersen, J. Z., Incerpi, S., Nana, A. W., Tang, H-Y., Lin, H-Y., Mousa, S. A., Davis, P. J., & Whang-Peng, J. (2019). Tetrac and NDAT Induce Anti-proliferation via Integrin αvβ3 in Colorectal Cancers With Different K-RAS Status. Frontiers in Endocrinology, 10(APR), 130. [130]. https://doi.org/10.3389/fendo.2019.00130