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

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 ofHBE1in 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 ofHBE1was examined by assessing its impact on ROS levels, mitochondrial-mediated apoptosis, and ER stress pathways, includingIRE1α phosphorylationandGRP78 expression.

RESULTS

Overexpression ofHBE1was found to suppress ROS generation and inhibit mitochondrial-dependent apoptosis. Additionally, it attenuated ER stress by reducingIRE1α phosphorylationwhile upregulatingGRP78.

CONCLUSION

These findings demonstrate a strong correlation between elevatedHBE1expression and gemcitabine resistance in pancreatic cancer cells, suggesting its potential as a therapeutic target to overcome chemoresistance.