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Comparative analysis of NRF2-responsive gene expression in AcPC-1 pancreatic cancer cell line
1Department of Nanobiomedical Science, Graduate School, Dankook University, 119 Dandae-ro, Dongnam-gu, Cheonan-si, Chungnam 330-714 Republic of Korea.
Abstract:
NRF2 is a nuclear transcription factor activated in response to oxidative stress and related with metabolizing of xenotoxic materials and ABC transporter mediated drug resistance. We studied the expression of mRNAs under the siRNA-mediated knockdown of NRF2 and tBHQ-treated condition in AsPC-1 metastatic pancreatic cancer cell line to understand the AsPC-1 specific role(s) of NRF2 and further to investigate the relationship between drug resistance and metastatic plasticity and mobility of AsPc1. Here we show that the genes of aldo-keto reductases, cytochrome P450 family, aldehyde dehydrogenase, thioredoxin reductase, ABC transporter and epoxide hydrolase responsible for drug metabolism or oxidative stress concisely responded to NRF2 stabilization and knockdown of NRF2. In addition the expression of PIR, a candidate of oncogene and KISS1, a suppressor of metastasis were affected by NRF2 stabilization and knockdown. Our result provide comprehensive understanding of NRF2 target genes of drug response, oxidative stress response and metastasis in AsPc-1 metastatic pancreatic cancer cell line.
Insights
Nuclear factor erythroid 2-related factor 2 (NRF2) influences drug metabolism and metastasis in pancreatic cancer. This study clarifies NRF2
Area of Science:
- Molecular Biology
- Cancer Research
- Pharmacology
Background:
- Nuclear factor erythroid 2-related factor 2 (NRF2) is a transcription factor activated by oxidative stress.
- NRF2 plays a role in xenobiotic metabolism and drug resistance.
- Its specific functions in metastatic pancreatic cancer remain to be fully elucidated.
Purpose of the Study:
- To investigate the role of NRF2 in the AsPC-1 metastatic pancreatic cancer cell line.
- To understand the relationship between NRF2, drug resistance, and metastatic plasticity.
- To identify NRF2 target genes involved in drug metabolism, oxidative stress, and metastasis.
Main Methods:
- siRNA-mediated knockdown of NRF2 in AsPC-1 cells.
- Treatment with tBHQ to stabilize NRF2.
- mRNA expression analysis to assess gene responses.
Main Results:
- NRF2 modulation significantly affected the expression of genes involved in drug metabolism (e.g., aldo-keto reductases, cytochrome P450, aldehyde dehydrogenase, ABC transporters) and oxidative stress response.
- NRF2 stabilization and knockdown influenced the expression of the oncogene *PIR* and the metastasis suppressor *KISS1*.
- A comprehensive profile of NRF2 target genes related to drug response, oxidative stress, and metastasis in AsPC-1 cells was established.
Conclusions:
- NRF2 plays a critical role in regulating drug metabolism, oxidative stress, and metastatic processes in pancreatic cancer.
- Understanding NRF2's targets provides insights into potential therapeutic strategies for metastatic pancreatic cancer.
- This study enhances the comprehension of NRF2's multifaceted role in pancreatic cancer progression and drug resistance.
