Tetrac and NDAT Induce Anti-proliferation via Integrin αvβ3 in Colorectal Cancers With Different K-RAS Status

Yu-Tang Chin, Zong-Rong He, Chi-Long Chen, Hsiao-Ching Chu, Yih Ho, Po-Yu Su, Yu-Chen S H Yang, Kuan Wang, Ya-Jung Shih, Yi-Ru Chen, Jens Z Pedersen, Sandra Incerpi, André Wendindondé Nana, Heng-Yuan Tang, Hung-Yun Lin, Shaker A Mousa, Paul J Davis, Jacqueline Whang-Peng

研究成果: 雜誌貢獻文章

摘要

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 anti-proliferation 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 anti-proliferation 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.
原文英語
頁(從 - 到)130
期刊Frontiers in Endocrinology
10
DOIs
出版狀態已發佈 - 2019

指紋

Integrins
Colorectal Neoplasms
HCT116 Cells
Neoplasms
HT29 Cells
Preclinical Drug Evaluations
Drug Combinations
Taiwan
Thyroid Hormones
Drug Resistance
Heterografts
tetraiodothyroacetic acid
Cell Culture Techniques
Perfusion
Clinical Trials
Pharmaceutical Preparations

引用此文

Tetrac and NDAT Induce Anti-proliferation via Integrin αvβ3 in Colorectal Cancers With Different K-RAS Status. / Chin, Yu-Tang; He, Zong-Rong; Chen, Chi-Long; Chu, Hsiao-Ching; Ho, Yih; Su, Po-Yu; Yang, Yu-Chen S H; Wang, Kuan; Shih, Ya-Jung; Chen, Yi-Ru; Pedersen, Jens Z; Incerpi, Sandra; Nana, André Wendindondé; Tang, Heng-Yuan; Lin, Hung-Yun; Mousa, Shaker A; Davis, Paul J; Whang-Peng, Jacqueline.

於: Frontiers in Endocrinology, 卷 10, 2019, p. 130.

研究成果: 雜誌貢獻文章

Chin, Yu-Tang ; He, Zong-Rong ; Chen, Chi-Long ; Chu, Hsiao-Ching ; Ho, Yih ; Su, Po-Yu ; Yang, Yu-Chen S H ; Wang, Kuan ; Shih, Ya-Jung ; Chen, Yi-Ru ; Pedersen, Jens Z ; Incerpi, Sandra ; Nana, André Wendindondé ; Tang, Heng-Yuan ; Lin, Hung-Yun ; Mousa, Shaker A ; Davis, Paul J ; Whang-Peng, Jacqueline. / Tetrac and NDAT Induce Anti-proliferation via Integrin αvβ3 in Colorectal Cancers With Different K-RAS Status. 於: Frontiers in Endocrinology. 2019 ; 卷 10. 頁 130.
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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 anti-proliferation 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 anti-proliferation 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.",
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AU - Chin, Yu-Tang

AU - He, Zong-Rong

AU - Chen, Chi-Long

AU - Chu, Hsiao-Ching

AU - Ho, Yih

AU - Su, Po-Yu

AU - Yang, Yu-Chen S H

AU - Wang, Kuan

AU - Shih, Ya-Jung

AU - Chen, Yi-Ru

AU - Pedersen, Jens Z

AU - Incerpi, Sandra

AU - Nana, André Wendindondé

AU - Tang, Heng-Yuan

AU - Lin, Hung-Yun

AU - Mousa, Shaker A

AU - Davis, Paul J

AU - Whang-Peng, Jacqueline

PY - 2019

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N2 - 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 anti-proliferation 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 anti-proliferation 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.

AB - 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 anti-proliferation 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 anti-proliferation 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.

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