14 August 2019 : Laboratory Research
Irisin Enhances Doxorubicin-Induced Cell Apoptosis in Pancreatic Cancer by Inhibiting the PI3K/AKT/NF-κB PathwayJiayu Liu12ABCDEF, Yibing Huang12ACDF, Yu Liu3ACEG*, Yuxin Chen12ACEG
Med Sci Monit 2019; 25:6085-6096
BACKGROUND: Irisin, a myokine released from skeletal muscle following exercise, has been shown to affect the proliferation of some cancer cells and chemosensitivity of anticancer drugs like doxorubicin (DOX). However, the effects of irisin on chemosensitivity in pancreatic cancer (PC) cells have not been studied.
MATERIAL AND METHODS: In this study, the effects of irisin co-treatment with DOX or gemcitabine (GEM) on MIA PaCa-2, BxPC-3 PC cells, and H9c2 cardiomyocytes were investigated. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, flow cytometry, and TUNEL (TdT-mediated dUTP nick-end labeling) assays were conducted to evaluate cytotoxicity induced by DOX or GEM. Fluorescence microscopy and flow cytometry experiments were performed to assess the intracellular accumulation of DOX. Cellular levels of apoptosis-related protein expression and protein phosphorylation were determined by Western blot analyses.
RESULTS: The results showed that irisin can increase the chemosensitivity of PC cells to DOX or GEM. The analyses of apoptosis indicated that irisin enhances DOX-induced cellular apoptosis by increasing the expression of cleaved PARP (poly ADP-ribose polymerase) and cleaved caspase-3, and reducing the expression of B cell lymphoma/lewkmia-2 (BCL-2) and B cell lymphoma-extra large (BCL-xL) in PC cells but not in H9c2 cells. Irisin attenuated serine/threonine kinase AKT (protein kinase B/PKB) phosphorylation and inhibited the activation of nuclear factor κB (NF-κB) signaling in PC cells.
CONCLUSIONS: Irisin can potentiate the cytotoxicity of doxorubicin in PC cells without increasing cardiotoxicity, possibly through inactivating the PI3K/AKT/NF-κB signaling pathway.
Keywords: Apoptosis Inducing Factor, Doxorubicin, Pancreatic Neoplasms, Antineoplastic Combined Chemotherapy Protocols, Cell Death, Deoxycytidine, Drug Synergism, Fibronectins, Myocytes, Cardiac, Phosphatidylinositol 3-Kinases, Phosphorylation, Proto-Oncogene Proteins c-akt
01 February 2023 : EditorialEditorial: The XBB.1.5 (‘Kraken’) Subvariant of Omicron SARS-CoV-2 and its Rapid Global Spread
Med Sci Monit 2023; 29:e939580
19 January 2023 : Clinical ResearchEvaluation of Health-Related Quality of Life and Mental Health in 729 Medical Students in Indonesia During ...
Med Sci Monit In Press; DOI: 10.12659/MSM.938892
19 January 2023 : Clinical ResearchDetermining the Impact of the COVID-19 Pandemic on Dental Care in the Serbian Adult Population: An Online Q...
Med Sci Monit 2023; 29:e939238
27 December 2022 : Clinical ResearchEffect of Physiotherapy to Correct Rounded Shoulder Posture in 30 Patients During the COVID-19 Pandemic in ...
Med Sci Monit 2022; 28:e938926
03 Feb 2023 : Clinical ResearchTreatment of Gingival Recession Defects with Pouch and Tunnel Technique Using Connective Tissue Graft and L...
Med Sci Monit In Press; DOI: 10.12659/MSM.938865
02 Feb 2023 : Clinical ResearchOnline Questionnaire-Based Study to Evaluate the Attitudes and Use of Rubber Dental Dams by Saudi Dental Pr...
Med Sci Monit In Press; DOI: 10.12659/MSM.938672
02 Feb 2023 : Database AnalysisPrognostic-Related Biomarkers in Pancreatic Ductal Adenocarcinoma Correlating with Immune Infiltrates Based...
Med Sci Monit In Press; DOI: 10.12659/MSM.938785
Most Viewed Current Articles
13 Nov 2021 : Clinical ResearchAcceptance of COVID-19 Vaccination and Its Associated Factors Among Cancer Patients Attending the Oncology ...
Med Sci Monit 2021; 27:e932788
30 Dec 2021 : Clinical ResearchRetrospective Study of Outcomes and Hospitalization Rates of Patients in Italy with a Confirmed Diagnosis o...
Med Sci Monit 2021; 27:e935379
08 Mar 2022 : Review articleA Review of the Potential Roles of Antioxidant and Anti-Inflammatory Pharmacological Approaches for the Man...
Med Sci Monit 2022; 28:e936292