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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Dec 21, 2021 |
| Title |
Nrf2 depletion sensitizes pancreatic cancer cells to gemcitabine via aldehyde dehydrogenase 3a1 repression. |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
The central regulator of oxidative stress responses, Nrf2, is attracting great interest as a therapeutic target in various cancers. Explorations of novel Nrf2 inhibitors have been reported, which suggest future clinical applications. Halofuginone, the derivative of natural plant alkaloid, has been reported to deplete Nrf2 rapidly in cancer cells with Nrf2 activation. In the current study, we identified that halofuginone sensitizes pancreatic cancer cells to gemcitabine, both in vitro and in vivo settings. We identified downregulation of Aldh3a1 in mouse pancreatic cancer cell lines after halofuginone treatment. The Nrf2 inducer diethyl maleate treatment upregulated Aldh3a1, and Nrf2 deleted pancreatic cancer cell lines failed to show induction. Knockdown of Aldh3a1 also sensitized cancer cells to gemcitabine, suggesting contribution of Aldh3a1 to gemcitabine resistance as a downstream target of Nrf2. Current study confirmed the therapeutic benefits of halofuginone in pancreatic cancer.
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| Overall design |
Mouse cancer cell (K5, K6) were treated with control (DMSO) (K5C, K6C) or halofuginone at 100 nM for 24 hours (K5H, K6H). Gene expression profiles were compared between K5C and K5F, K6C and K6F, respectively.
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| Contributor(s) |
Hamada S |
| Citation(s) |
34321315 |
| Submission date |
Apr 14, 2021 |
| Last update date |
Dec 23, 2021 |
| Contact name |
Shin Hamada |
| Organization name |
Tohoku University Graduate School of Medicine
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| Department |
Division of Gastroenterology
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| Street address |
1-1 Seiryo-machi, Aobaku
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| City |
Sendai |
| State/province |
Miyagi |
| ZIP/Postal code |
9808574 |
| Country |
Japan |
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| Platforms (1) |
| GPL21163 |
Agilent-074809 SurePrint G3 Mouse GE v2 8x60K Microarray [Probe Name version] |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA721874 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE172046_RAW.tar |
61.7 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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