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Rhenium Perrhenate (188ReO4) Induced Apoptosis and Reduced Cancerous Phenotype in Liver Cancer Cells

Title	Rhenium Perrhenate (188ReO4) Induced Apoptosis and Reduced Cancerous Phenotype in Liver Cancer Cells
Authors	Samieh Asadian, Abbas Piryaei, Nematollah Gheibi, Bagher Aziz Kalantari, Mohamad Reza Davarpanah, Mehdi Azad, Valentina Kapustina, Mehdi Alikhani, Sahar Moghbeli Nejad, Hani Keshavarz Alikhani, Morteza Mohamadi, Anastasia Shpichka, Peter Timashev, Moustapha Hassan, Massoud Vosough
Magazine	Cells
Date	01/17/2022
DOI	10.3390/cells11020305
Introduction	Hepatocellular carcinoma (HCC) recurrence following conventional treatment poses a significant challenge. While advancements have been achieved in targeted therapies, HCC remains the fourth leading cause of cancer mortality globally. Radionuclide therapy emerges as a promising targeted strategy. Rhenium-188 (188Re), a β-emitting radionuclide, is applied in clinical settings to trigger apoptosis and inhibit cell proliferation. Despite the efficiency of adherent cell cultures, they often lack proper cell-cell and cell-extracellular matrix interactions. This study evaluates 188Re's potential as a therapeutic agent for HCC in both 2D and 3D models. Viability assays revealed that treated Huh7 and HepG2 cell lines exhibited significantly higher death rates compared to untreated controls. Following 188ReO4 treatment, Annexin/PI assays demonstrated substantial apoptosis in HepG2 cells after 48 hours, whereas Huh7 cells did not respond similarly. Quantitative RT-PCR and western blot analyses confirmed increased apoptosis due to 188ReO4 treatment. Huh7 cells exposed to effective 188ReO4 doses experienced cell cycle arrest in the G2 phase. Colony formation assays further demonstrated growth suppression in Huh7 and HepG2 cells post-treatment. Immunostaining revealed inhibited proliferation in 188ReO4-treated cells on 3D liver ECM scaffolds. The PI3-AKT signalling pathway was activated in 3D but not 2D cultures. In vivo experiments with nude mice showed that Huh7 cells treated with effective 188ReO4 doses lost tumour formation ability compared to controls. These results indicate that 188ReO4 is a promising therapeutic agent against HCC by inducing apoptosis, enforcing cell cycle arrest, and preventing tumour formation. This approach could be effectively combined with antibodies and peptides for more selective and personalised therapies.
Quote	Samieh Asadian, Abbas Piryaei and Nematollah Gheibi et al. Rhenium Perrhenate (188ReO4) Induced Apoptosis and Reduced Cancerous Phenotype in Liver Cancer Cells. Cells. 2022. Vol. 11(2):305. DOI: 10.3390/cells11020305
Materials	Chemical Compounds
Industry	Pharmaceutical Industry

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