Crosstalk between ER-stress and apoptosis in irradiated HepG2 cells with gemcitabine: implication of PI3K/AKT and IκB/NF-κB signaling pathways. Issue 1 (1st January 2020)

• Record Type: Journal Article
• Authors: Moustafa, Enas Mahmoud; Rashed, Laila Ahmed; El-Sebaie, Mohammed M.; Thabet, Noura Magdy; Abdel-Rafei, Mohamed Khairy
• Is Part Of: Journal of Radiation Research and Applied Sciences. Volume 13:Issue 1(2020)
• Page Start: 144
• Page End: 154
• Publication Date: 2020-01-01
• Subjects: HepG2 cell line -- gemcitabine -- γ-radiation -- ER stress -- IκB/NF-κB and Caspase-3; Ionizing radiation -- Periodicals; Nuclear physics -- Periodicals; Radiation; Radiation; Periodicals; 539.7
• DOI: 10.1080/16878507.2020.1715569
• Languages: English
• ISSNs: 1687-8507

Abstract

ABSTRACT: Gemcitabine (GEM) is an anti-cancer drug that has been used in the treatment of a wide range of human cancers. However, cancer cells developing resistance to GEM which may limit its use. So, adjuvant therapies either enhance the effects of GEM or overcome resistance are needed for the treatment of cancer. In this study, we examined the influence of the interaction between γ-radiation (RAD) and GEM against HepG2 cells acquired resistance to GEM. Based on our data, the combination therapy elevates ROS production, induces endoplasmic reticulum (ER)-stress response machinery, up-regulates caspase-3 and p53 as well as boosts PTEN proficiency which blocked PI3K/AKT pathway that inhibits IκB/NF-κB signaling. It could be concluded that therapeutic strategies of gemcitabine in cancer might be potentiated by radiotherapy to reach better therapeutic outcomes.