Tiliroside Combined with Anti-MUC1 Monoclonal Antibody as Promising Anti-Cancer Strategy in AGS Cancer Cells

Area of Science:

• Biochemistry and Molecular Biology
• Cancer Research
• Glycobiology

Background:

• Altered mucin-type O-glycosylation, including truncated O-glycans and altered fucosylation, is prevalent in gastric cancer, promoting tumor development.
• MUC1, a key glycoprotein, is frequently overexpressed and aberrantly glycosylated in various cancers.
• Tiliroside, a dietary flavonoid, exhibits anti-cancer properties.

Purpose of the Study:

• To evaluate the synergistic effects of anti-MUC1 therapy combined with tiliroside on gastric cancer cells.
• To investigate the impact of this combined treatment on MUC1 expression, tumor-associated antigens, and key signaling pathways.

Main Methods:

• AGS gastric cancer cells were treated with varying concentrations of tiliroside, anti-MUC1 monoclonal antibody (mAb), or a combination of both.
• Gene expression analysis using Real-Time PCR for MUC1, glycosyltransferases (C1GalT1, ST3GalT1, FUT4), Gal-3, Akt, and NF-κB.
• Protein expression analysis via ELISA and Western blotting for MUC1, Tn antigen, and sialyl T antigen.

Main Results:

• Anti-MUC1 mAb treatment significantly reduced MUC1 expression.
• The combination of anti-MUC1 and tiliroside demonstrated superior efficacy over monotherapy in downregulating C1GalT1, ST3GalT1, FUT4, Gal-3, NF-κB, and Akt mRNA levels.
• Combined therapy also led to a more pronounced reduction in the expression of tumor-associated Tn and sialyl T antigens compared to individual treatments.

Conclusions:

• The combined administration of anti-MUC1 and tiliroside exhibits enhanced anti-cancer activity against gastric cancer cells.
• This synergistic effect is mediated by the modulation of key glycosylation enzymes, signaling molecules, and tumor-associated antigens.
• The developed combined therapy strategy holds significant promise for future anti-gastric cancer treatments.