Targeting Glypican-1 Reverses Resistance to 5-Fluorouracil in Esophageal Adenocarcinoma Cells

Abstract

Background/aim: The primary mode of therapy for individuals with locally advanced esophageal adenocarcinoma (EAC) is neoadjuvant chemotherapy, commonly 5-Fluorouracil (5-FU). However, approximately 30% of these patients develop resistance to therapy. Glypican-1 (GPC-1) has been identified as one of the key drivers of chemoresistance in cancer; however, its role in EAC cells has not been explored. The objective of the present study was to evaluate the role of GPC-1 in chemoresistance to 5-FU in EAC cells.

Materials and methods: Cell viability to 5-FU was measured with CCK-8 assay, and GPC-1 expression was validated using western blot. 5-FU resistant cell lines were generated. The effect of lentivirus-mediated GPC-1 knockdown on FLO-1 cell viability, cell cycle, and apoptosis was evaluated.

Results: 5-FU resistant EAC cells showed increased GPC-1 expression and knockdown of GPC-1 increased cell death and apoptosis. Importantly, the knockdown of GPC-1 enhanced the antitumor effects of 5-FU in vitro via down-regulating AKT/ERK/β-catenin signaling.

Conclusion: Silencing GPC-1 has the potential to augment the efficacy of 5-FU chemotherapy in resistant EAC tumors.

Keywords: 5-fluorouracil; Glypican-1; chemo-sensitization; drug resistance; esophageal adenocarcinoma; shRNA.