The effect of HBE1 on resistance to gemcitabine in pancreatic cancer cells

IF 1.3 4区医学 Q4 GASTROENTEROLOGY & HEPATOLOGY

Arab Journal of Gastroenterology Pub Date : 2026-05-01 Epub Date: 2026-03-15 DOI:10.1016/j.ajg.2026.01.006

Jiyun Cheng , Haixing Jiang , Xianen Yu , Peining Huang , Yihan Lu , Shudan Tan , Xiaojun Liu , Shanyu Qin

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引用次数: 0

Abstract

Background

Chemotherapy resistance remains a major challenge in pancreatic cancer treatment, with gemcitabine-based therapy being a primary approach. However, the mechanisms underlying gemcitabine resistance in pancreatic cancer cells are not yet fully understood. This study aimed to investigate the role of HBE1 in conferring resistance to gemcitabine and explore its effects on reactive oxygen species (ROS) production, mitochondrial apoptosis, and endoplasmic reticulum (ER) stress.

Materials and methods

A gemcitabine-resistant pancreatic cancer cell line was systematically developed through gradual, six-month exposure to increasing concentrations of gemcitabine. The role of HBE1 was examined by assessing its impact on ROS levels, mitochondrial-mediated apoptosis, and ER stress pathways, including IRE1α phosphorylation and GRP78 expression.

Results

Overexpression of HBE1 was found to suppress ROS generation and inhibit mitochondrial-dependent apoptosis. Additionally, it attenuated ER stress by reducing IRE1α phosphorylation while upregulating GRP78.

Conclusion

These findings demonstrate a strong correlation between elevated HBE1 expression and gemcitabine resistance in pancreatic cancer cells, suggesting its potential as a therapeutic target to overcome chemoresistance.

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HBE1在胰腺癌细胞对吉西他滨耐药中的作用。

背景：化疗耐药仍然是胰腺癌治疗的主要挑战，以吉西他滨为基础的治疗是主要方法。然而，胰腺癌细胞对吉西他滨耐药的机制尚不完全清楚。本研究旨在探讨hbe1在吉西他滨耐药中的作用，并探讨其对活性氧（ROS）产生、线粒体凋亡和内质网（ER）应激的影响。材料和方法：通过逐渐暴露于增加吉西他滨浓度的六个月，系统地开发了一种耐吉西他滨胰腺癌细胞系。通过评估其对ROS水平、线粒体介导的凋亡和内质网应激途径（包括ire1 α磷酸化和grp78表达）的影响，研究了hbe1的作用。结果：hbe1过表达可抑制ROS生成，抑制线粒体依赖性细胞凋亡。此外，它通过降低ire1 α磷酸化和上调grp78来减轻内质网应激。结论：这些发现表明胰腺癌细胞中hbe1表达升高与吉西他滨耐药之间存在很强的相关性，提示其有可能成为克服化疗耐药的治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Arab Journal of Gastroenterology Medicine-Gastroenterology

CiteScore

2.70

自引率

0.00%

发文量

期刊介绍： Arab Journal of Gastroenterology (AJG) publishes different studies related to the digestive system. It aims to be the foremost scientific peer reviewed journal encompassing diverse studies related to the digestive system and its disorders, and serving the Pan-Arab and wider community working on gastrointestinal disorders.