Potential anti-tumor activity of 13.56 MHz alternating magnetic hyperthermia and chemotherapy on the induction of apoptosis in human colon cancer cell lines HT29 and HCT116 by up-regulation of Bax, cleaved caspase 3&9, and cleaved PARP proteins

Cancer Nanotechnology

Majid Safa¹  Sepideh Khoee²  Sakine Shirvalilou³  Samideh Khoei⁴  Vahid Pirhajati Mahabadi⁵  Saba Jahangiri⁶ 

[1] Department of Hematology and Blood Transfusion, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran;Department of Polymer Chemistry, School of Chemistry, College of Science, University of Tehran, Tehran, Iran;Finetech in Medicine Research Center, Iran University of Medical Sciences, P.O. Box: 1449614525, Tehran, Iran;Finetech in Medicine Research Center, Iran University of Medical Sciences, P.O. Box: 1449614525, Tehran, Iran;Department of Medical Physics, School of Medicine, Iran University of Medical Sciences, Tehran, Iran;Neuroscience Research Center, Iran University of Medical Sciences, Tehran, Iran;Student Research Committee, Iran University of Medical Sciences, Tehran, Iran;Department of Medical Physics, School of Medicine, Iran University of Medical Sciences, Tehran, Iran;

关键词: Colon cancer;    5-fluorouracil;    Magnetic hyperthermia;    Apoptosis;    Cleaved caspase;    Cleaved PARP;    Pro-PARP proteins;   

DOI  :  10.1186/s12645-021-00108-5

来源: Springer

【 摘 要 】

BackgroundThe purpose of the present study was to evaluate the efficacy of chemo-magnetic hyperthermia (MH), a combination of alternating magnetic field (AMF) and superparamagnetic nanoparticles (SPIONs) coated with Polyethylene glycol-Poly(butyl acrylate)-Polyethylene glycol (PEG-PBA-PEG) carrying 5-Fluorouracil (5-Fu), at inducing apoptosis in the human cancer cell lines HT29 and HCT116. This process can be mediated by alterations in the expression of apoptotic effector proteins, including Bax, Bcl-2, cleaved caspase 3&9, and cleaved PARP, which are involved in the intrinsic pathway of apoptosis. For this purpose, the cells were cultured as monolayers. Then both cell lines were treated with 5-Fu/magnetic nanoparticles and magnetic hyperthermia. Finally, the effect of treatment on cancer cells was determined by Western blot analysis and flow cytometry.ResultsOur results showed that combined chemo-magnetic thermotherapy significantly increased the apoptosis in colon cancer cells compared to chemotherapy or hyperthermia alone (P < 0.05). Up-regulation of Bax, cleaved caspase 3&9, and cleaved PARP proteins was indicative of apoptosis induction in cancer cells, which are involved in the intrinsic pathway of apoptosis.ConclusionsThis study demonstrates that localized hyperthermia was able to significantly trigger the 5-Fu release and inhibit cell viability, which, due to the synchronization of hyperthermia and chemotherapy, exacerbated the damage of cancer cells.Graphical Abstract

【 授权许可】

CC BY