靶向 GPC-1 逆转食管腺癌细胞对 5-氟尿嘧啶的耐药性。

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

机构信息

Division of Gastrointestinal Tumor and Endocrine Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO, U.S.A.;

Division of Gastrointestinal Tumor and Endocrine Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO, U.S.A.

出版信息

Anticancer Res. 2023 Aug;43(8):3411-3418. doi: 10.21873/anticanres.16516.

DOI:10.21873/anticanres.16516

PMID:37500147

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.

摘要

背景/目的：局部晚期食管腺癌（EAC）患者的主要治疗模式是新辅助化疗，通常是氟尿嘧啶（5-FU）。然而，大约 30%的患者对治疗产生耐药性。磷脂酰聚糖-1（GPC-1）已被确定为癌症中化学耐药性的关键驱动因素之一；然而，其在 EAC 细胞中的作用尚未得到探索。本研究的目的是评估 GPC-1 在 EAC 细胞对 5-FU 化学耐药性中的作用。