Dataset Information

Tetrac and NDAT Induce Anti-proliferation via Integrin ?v?3 in Colorectal Cancers With Different K-RAS Status.

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 ?v?3 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 ?v?3, 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.

SUBMITTER: Chin YT

PROVIDER: S-EPMC6422911 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Tetrac and NDAT Induce Anti-proliferation via Integrin αvβ3 in Colorectal Cancers With Different <i>K-RAS</i> Status.

Chin Yu-Tang YT He Zong-Rong ZR Chen Chi-Long CL Chu Hsiao-Ching HC Ho Yih Y Su Po-Yu PY Yang Yu-Chen S H YSH Wang Kuan K Shih Ya-Jung YJ Chen Yi-Ru YR Pedersen Jens Z JZ Incerpi Sandra S Nana André Wendindondé AW Tang Heng-Yuan HY Lin Hung-Yun HY Mousa Shaker A SA Davis Paul J PJ Whang-Peng Jacqueline J

Frontiers in endocrinology 20190312

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 <i>in vitro</i> and in xenograft model of different neoplasms, including colorectal cancer ...[more]

PMID: 30915033

Similar Datasets

Project description:Heatmap, pathway scores and significant modulation of genes induced by heteronemin, tetrac, and their combination versus the control in HCT 116 cells were performed. (abstract) Overexpression of EGFR accounts for 60-80% of colorectal cancer patients. Anti-EGFR monoclonal antibodies are ineffective in colorectal cancer patients due to KRAS mutation. To discover new therapeutic strategies urgently need for colorectal cancer patients. Sponge extract, heteronemin, has been shown to induce anti-proliferation in different types of cancer. Tetrac shows to inhibit Ras-mutant cancer cell proliferation. Cell viability was evaluated in the HT-29 and HCT-116 cell lines to determine the antitumor effects of heteronemin and its combination with tetrac. Gene expressions were determined by NanoString technology and a quantitative RT-PCR. Protein expressions and cell cycle distributions were respectively assessed by Western blotting and flow cytometry. Heteronemin or its combination with tetrac inhibited cancer cell growth in both mutant and KRAS wild-type CRC. Combined treatment altered the cell cycle in both cell lines at the sub-G1 and S phases. Moreover, their combination induced inactivation of EGFR signaling via downregulating the phosphorylated and total extracellular signal-regulated kinase 1/2 (ERK1/2) protein in both cell lines. The programmed death ligand 1 (PD-L1) protein was reduced in HCT-116 cells, while HT-29 cells showed downregulation of the phosphorylated and total phosphatidylinositol 3-kinase (PI3K) protein. In KRAS mutant cells, heteronemin or its combination with tetrac showed significant modulation of genes associated with cancer progression by NanoString technology. Therefore, tetrac improved the anticancer effect of heteronemin and may be an alternative strategy to effective overcome KRAS mutation-acquired resistance to anti-EGFR therapy. 1. To investigate whether heteronemin combined tetrac induce the antitumor effect in different KRAS statuses of CRC via blocking of EGFR signaling cascades. 2. To assess gene expression profiling in KRAS-mutant CRC cells by nanostring technology.

Dataset Information

Tetrac and NDAT Induce Anti-proliferation via Integrin ?v?3 in Colorectal Cancers With Different K-RAS Status.

Publications

Tetrac and NDAT Induce Anti-proliferation via Integrin αvβ3 in Colorectal Cancers With Different <i>K-RAS</i> Status.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets