PFKFB3 deprivation attenuates the cisplatin resistance via blocking its autophagic elimination in colorectal cancer cells
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View abstract on PubMed
Summary
This summary is machine-generated.Inhibition of 6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase isoform 3 (PFKFB3) reverses cisplatin resistance in colorectal cancer by reducing DDP-induced autophagy. This finding highlights PFKFB3 as a potential therapeutic target for overcoming chemoresistance.
Area Of Science
- Oncology
- Molecular Biology
- Biochemistry
Background
- 6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase isoform 3 (PFKFB3) is upregulated in various cancers and implicated in chemoresistance.
- The precise mechanisms underlying PFKFB3's role in chemoresistance, particularly to cisplatin (DDP), remain incompletely understood.
Purpose Of The Study
- To investigate the role of PFKFB3 in cisplatin resistance in colorectal cancer (CRC).
- To explore the interplay between PFKFB3, autophagy, and DDP response in CRC cells.
- To evaluate the therapeutic potential of PFKFB3 inhibition in reversing DDP resistance.
Main Methods
- Comparative analysis of DDP response in wild-type and DDP-resistant (DDR) CRC cells.
- Utilized coumarin-conjugated DDP (CP-DDP) to track DDP distribution.
- Employed pharmacological and genetic inhibition of autophagy and PFKFB3.
- Validated findings in a mouse xenograft model.
Main Results
- DDR cells exhibited reduced apoptosis, elevated autophagy, and higher PFKFB3 levels upon DDP treatment.
- CP-DDP co-localized with LC3 (autophagy marker), with faster clearance in DDR cells.
- Simultaneous inhibition of autophagy and PFKFB3 attenuated CP-DDP elimination and reversed DDP resistance.
- PFKFB3 inhibition decreased DDP-induced autophagy and, when combined with DDP, significantly reduced tumor growth *in vivo*.
Conclusions
- PFKFB3 inhibition mitigates DDP-induced autophagy, enhancing DDP retention and efficacy.
- Targeting PFKFB3 is a promising strategy to overcome cisplatin resistance in colorectal cancer.
- PFKFB3 represents a viable therapeutic target for improving CRC treatment outcomes.
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