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| Status |
Public on Sep 01, 2024 |
| Title |
Heteronemin and Tetrac Induce Anti-proliferation by Blocking EGFR-mediated Signaling in Colorectal Cancer Cells |
| Organism |
Homo sapiens |
| Experiment type |
Other
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| Summary |
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.
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| Overall design |
In this study, NanoString was used for the gene expression analyses of the HCT-116 cell line.Technical and biological normalization of the raw counts of each gene was performed using nSolver Software vers. 4.0. For technical normalization, a positive control factor was calculated for each sample.
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| Contributor(s) |
Unson S, Tsai B |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
Sep 09, 2021 |
| Last update date |
Sep 01, 2024 |
| Contact name |
Sukanya Unson |
| E-mail(s) |
sukanya_unson@hotmail.com
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| Organization name |
Taipei medical university
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| Department |
Cancer biology and drug discovery
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| Street address |
No. 250, Wuxing Street, Xinyi District
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| City |
Taipei City |
| ZIP/Postal code |
110 |
| Country |
Taiwan |
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| Platforms (1) |
| GPL26599 |
nCounter PanCancer Progression panel |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA762009 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE183782_RAW.tar |
120.0 Kb |
(http)(custom) |
TAR (of RCC) |
| GSE183782_geo_submission_RatioData.csvHeteronemin+Tetrac.csv.gz |
12.7 Kb |
(ftp)(http) |
CSV |
| GSE183782_geo_submission_RatioData.csvHeteronemin.csv.gz |
13.3 Kb |
(ftp)(http) |
CSV |
| GSE183782_geo_submission_RatioData.csvTetrac.csv.gz |
12.7 Kb |
(ftp)(http) |
CSV |
| Processed data included within Sample table |
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