Exploring the Anti-Colorectal Cancer Mechanism of Norcantharidin Through TRAF5/NF-κB Pathway Regulation and...

Area of Science:

• Oncology
• Pharmacology
• Molecular Biology

Background:

• Colorectal cancer is a major global health concern.
• Cantharidin (CTD) derivatives, like norcantharidin (NCTD), show antitumor potential with reduced toxicity.
• The precise mechanism of NCTD in colorectal cancer treatment is not fully understood.

Purpose of the Study:

• To elucidate the mechanism of NCTD action in colorectal cancer.
• To identify key molecular targets of NCTD.
• To evaluate the efficacy of folate-receptor-targeting NCTD liposomes (FA-NCTD) for colorectal cancer therapy.

Main Methods:

• In vitro studies using HCT116 and HT-29 colorectal cancer cell lines.
• In vivo studies in colorectal cancer models.
• Whole-transcriptome sequencing and bioinformatics analysis.
• Design and assessment of folate-receptor-targeting NCTD liposomes (FA-NCTD).

Main Results:

• NCTD inhibited colorectal cancer cell viability, proliferation, and migration.
• NCTD induced apoptosis, altered cell cycle, mitochondrial potential, and increased reactive oxygen species.
• Whole-transcriptome analysis identified TRAF5 as a key target, with NCTD regulating the TRAF5/NF-κB pathway.
• FA-NCTD liposomes demonstrated effective tumor targeting and significantly inhibited tumor growth in vivo.

Conclusions:

• NCTD suppresses colorectal cancer proliferation by modulating the TRAF5/NF-κB pathway and inducing apoptosis.
• FA-NCTD liposomes offer a promising strategy for targeted colorectal cancer treatment with controlled release.