Curcumin Modulates 5-fluorouracil Sensitivity in Colorectal Cancer Cells Through the circ-NRIP1/miR-195-5p/SMURF1/AKT...

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Curcumin exhibits antitumor properties and potential as an adjunct cancer therapy.
• 5-fluorouracil (5-FU) chemotherapy is standard for colorectal cancer (CRC), but chemoresistance limits its efficacy.
• The precise mechanisms of curcumin in combination with chemotherapy, particularly concerning 5-FU resistance in CRC, require further elucidation.

Purpose of the Study:

• To investigate curcumin's role in modulating 5-FU sensitivity in CRC.
• To explore the underlying molecular mechanisms by which curcumin affects 5-FU resistance.
• To identify potential therapeutic targets for overcoming chemoresistance in CRC.

Main Methods:

• In vivo and in vitro validation of curcumin's antitumor effects.
• Identification of circ-NRIP1 as a direct target of curcumin in CRC cells.
• Mechanistic studies involving miRNA sequencing, Western blotting, and apoptosis assays to elucidate the circ-NRIP1/miR-195-5p/SMURF1/AKT pathway.

Main Results:

• Curcumin demonstrated synergistic antitumor efficacy with 5-FU in CRC models.
• Curcumin enhances 5-FU sensitivity by downregulating circ-NRIP1 expression.
• Curcumin disrupts the circ-NRIP1/miR-195-5p/SMURF1 axis, inhibiting AKT pathway activation and promoting apoptosis, thereby overcoming 5-FU resistance.

Conclusions:

• Curcumin effectively modulates 5-FU sensitivity in colorectal cancer through the circ-NRIP1/miR-195-5p/SMURF1/AKT regulatory pathway.
• Targeting circ-NRIP1 with curcumin presents a novel therapeutic strategy to enhance chemotherapy efficacy in CRC.
• These findings offer a promising approach for overcoming chemoresistance and improving clinical outcomes in CRC patients.