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Updated: Feb 13, 2026

Orthotopic Mouse Model of Colorectal Cancer
Published on: December 4, 2007
MiR-29b reverses oxaliplatin-resistance in colorectal cancer by targeting SIRT1
1Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
Abstract:
Oxaliplatin is a commonly used chemotherapeutic drug for the treatment of advanced colorectal cancer. However, acquired drug resistance against oxaliplatin remains a major obstacle for efficient use of it, and mechanisms underlying oxaliplatin resistance are still required to be explored. In the present study, we exposed colorectal cancer cell line SW480 to oxaliplatin for a long time to obtain oxaliplatin-resistant colorectal cancer cell model (OR-SW480). We found that intracellular expression of miR-29b was decreased when the SW480 cells became oxaliplatin-resistant. More importantly, overexpression of miR-29b resensitized OR-SW480 cells to oxaliplatin treatment. Mechanically, gene of SIRT1 was identified to be the target of miR-29b. Overexpression of miR-29b in oxaliplatin-treated OR-SW480 decreased the expression of SIRT1 to enhance the ROS production and JNK phosphorylation, and thus promoting apoptosis via activation of caspase 9, 7 and 3. On the other hand, expression plasmid of SIRT1, N-acetyl cysteine or SP600125 (JNK specific inhibitor) abolished the effect of miR-29b on oxaliplatin-treated OR-SW480. We therefore demonstrated that miR-29b reverses oxaliplatin-resistance in colorectal cancer by targeting SIRT1/ROS/JNK pathway.
Insights
MicroRNA-29b (miR-29b) can overcome oxaliplatin resistance in colorectal cancer. Restoring miR-29b levels targets SIRT1, enhancing apoptosis and improving treatment efficacy.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Oxaliplatin is a key chemotherapy for advanced colorectal cancer.
- Acquired resistance to oxaliplatin limits its effectiveness.
- Mechanisms of oxaliplatin resistance require further investigation.
Purpose of the Study:
- To explore mechanisms of oxaliplatin resistance in colorectal cancer.
- To investigate the role of miR-29b in oxaliplatin resistance.
- To identify therapeutic strategies to overcome oxaliplatin resistance.
Main Methods:
- Established an oxaliplatin-resistant colorectal cancer cell line (OR-SW480).
- Assessed miR-29b expression levels in resistant cells.
- Investigated the effect of miR-29b restoration on oxaliplatin sensitivity.
- Identified SIRT1 as a direct target of miR-29b.
- Analyzed the SIRT1/ROS/JNK pathway and apoptosis markers.
Main Results:
- Intracellular miR-29b expression was significantly decreased in OR-SW480 cells.
- Overexpression of miR-29b resensitized OR-SW480 cells to oxaliplatin.
- miR-29b directly targets and downregulates SIRT1 expression.
- miR-29b restoration increased ROS production and JNK phosphorylation.
- miR-29b promoted apoptosis via caspase activation.
Conclusions:
- miR-29b plays a crucial role in reversing oxaliplatin resistance in colorectal cancer.
- The miR-29b/SIRT1/ROS/JNK pathway is a novel mechanism underlying oxaliplatin resistance.
- Targeting miR-29b offers a potential therapeutic strategy to enhance oxaliplatin efficacy.
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