{"title":"Preclinical Aspects of [<sup>89</sup>Zr]Zr-DFO-Rituximab: A High Potential Agent for Immuno-PET Imaging.","authors":"Zahra Rohollahi, Seyed Mahmoud Reza Aghamiri, Hassan Yousefnia, Behrouz Alirezapour, Ali Moghaddasi, Samaneh Zolghadri","doi":"10.2174/0118744710326742241018050220","DOIUrl":"10.2174/0118744710326742241018050220","url":null,"abstract":"<p><strong>Background: </strong>An early diagnosis of cancer can lead to choosing more effective treatment and increase the number of cancer survivors. In this study, the preparation and preclinical aspects of [<sup>89</sup>Zr]Zr-DFO-Rituximab, a high-potential agent for PET imaging of Non- Hodgkin Lymphoma (NHL), were evaluated.</p><p><strong>Methods: </strong>DFO was conjugated to rituximab monoclonal antibody (mAb), and DFO-rituximab was successfully labeled with zirconium-89 (<sup>89</sup>Zr) at optimized conditions. The stability of the complex was assessed in human blood serum and PBS buffer. Radioimmunoreactivity (RIA) of the radioimmunoconjugate (RIC) was evaluated on CD20-overexpressing Raji cell line and CHO cells. The biodistribution of the radiolabeled mAb was studied in normal and tumorbearing rodents. Finally, the absorbed dose in human organs was estimated.</p><p><strong>Results: </strong>The radiolabeled compound was prepared with radiochemical purity (RCP) >99% (RTLC) and a specific activity of 180±1.8 GBq/g. The RCP of the final complex PBS buffer and human blood serum was higher than 95%, even after 48 h post incubation. The RIA assay demonstrated that more than 63% of the radiolabeled compound (40 ng/ml, 0.5 mL) was bound to 5×10<sup>6</sup> Raji cells. The biodistribution of the final product in tumor-bearing mice showed a high accumulation of the RIC in the tumor site in all intervals post-injection. Tumor/non-target ratios were increased over time, and longer imaging time was suggested. The dosimetry data indicated that the liver received the most absorbed dose after the complex injection.</p><p><strong>Conclusion: </strong>[<sup>89</sup>Zr]Zr-DFO-Rituximab represents a significant advancement in the field of oncological imaging and offers a robust platform for both diagnostic and therapeutic applications in the management of B-cell malignancies.</p>","PeriodicalId":10991,"journal":{"name":"Current radiopharmaceuticals","volume":" ","pages":"131-140"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Apigenin's Influence on Inflammatory and Epigenetic Responses in Rat Lungs After Radiotherapy.","authors":"Fatemeh Rajabinasab, Pooya Hajimirzaei, Fatemeh Ramezani, Fariborz Moayer, Fazel Gorjipour, Alireza Nikoofar, Leila Hassanzadeh, Michael R Hamblin, Atousa Janzadeh, Reza Paydar","doi":"10.2174/0118744710336823241011095632","DOIUrl":"10.2174/0118744710336823241011095632","url":null,"abstract":"<p><strong>Introduction: </strong>The lung is a moderately radio-sensitive organ. When cells are damaged due to accidental radiation exposure or treatment, they release molecules that lead to the recruitment of immune cells, accumulating inflammatory cytokines at the site of damage. Apigenin (Api) is a natural flavonoid known for its anti-inflammatory properties. In this study, we investigated the radioprotective properties of Api in the lung.</p><p><strong>Methods: </strong>Thirty-six Wistar rats were randomly assigned to nine groups: control, radiation (Rad), CMC+Rad, Api10+Rad, and Api20+Rad. Api was administered with an intraperitoneal injection for 7 days, after which the rats were irradiated with 6 Gy whole-body X-ray. At 6 and 72 hours post-irradiation, the rats were euthanized, and their lung tissue was extracted.</p><p><strong>Results: </strong>Radiation led to increased alveolar wall thickness and the infiltration of macrophages and lymphocytes. Furthermore, the expression levels of inflammatory factors such as a nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-κB), Glycogen synthase kinase-3 beta (GSK-3β), transforming growth factor-beta1 (TGF-β1), and epigenetic factors including DNA methyltransferase 3a (DNMT3a) and Histone deacetylase 2 (HDAC2) were elevated in the lung tissue following radiation. Meanwhile, the expression level of IκB-α decreased. However, administration of Api (at both 10&20 mg/kg) reversed the adverse effects of radiation.</p><p><strong>Conclusion: </strong>Api administration mitigated radiation-induced lung damage by reversing inflammatory and epigenetic changes.</p>","PeriodicalId":10991,"journal":{"name":"Current radiopharmaceuticals","volume":" ","pages":"147-157"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ozum Atasoy, Elvan Anadol, Atiye Seda Yar Saglam, Eyub Yasar Akdemir, Yasemin Sengun Coskun, Ece Atak, Sefika Dincer, Duygu Deniz Usta, Aslı Emniyet Sert, Gulnur Take Kaplanoglu, Yıldız Guney
{"title":"Synergistic Potential of GLP-1 Receptor Agonists and Radiotherapy in Breast Cancer Treatment: A New Therapeutic Avenue (TROD-GROG 006).","authors":"Ozum Atasoy, Elvan Anadol, Atiye Seda Yar Saglam, Eyub Yasar Akdemir, Yasemin Sengun Coskun, Ece Atak, Sefika Dincer, Duygu Deniz Usta, Aslı Emniyet Sert, Gulnur Take Kaplanoglu, Yıldız Guney","doi":"10.2174/0118744710381356250429045716","DOIUrl":"10.2174/0118744710381356250429045716","url":null,"abstract":"<p><strong>Introduction: </strong>GLP-1 receptor agonists (GLP-1 RAs) are anti-diabetic agents known for their anti-inflammatory and antioxidant properties. This study investigates the synergistic effects of GLP-1 RAs and radiotherapy (RT) on breast cancer in a preclinical mouse model.</p><p><strong>Materials and methods: </strong>Female BALB/c mice were inoculated with 4T1 breast cancer cells and divided into five groups: control, placebo, GLP-1 RA alone, RT alone, and combination treatment. GLP-1 RA was administered intraperitoneally, and a single 8 Gy RT dose was applied. Tumor volumes, histopathological changes, cytokine expression, and apoptosis-related protein profiles were evaluated. In vitro, 4T1 cell viability was assessed following GLP-1 RA and/or RT exposure.</p><p><strong>Results: </strong>Combination therapy significantly reduced tumor volume compared to RT or GLP-1 RA alone. Histological analysis revealed improved tissue morphology with the combined approach. Immunohistochemical staining showed decreased expression of pro-inflammatory markers (IL-6, TNF-α) and angiogenic factors (VEGF-A, FGF-2), while pro-apoptotic proteins (caspase-3, BAD, p53) were elevated. In vitro findings confirmed a synergistic reduction in cell viability with combined treatment.</p><p><strong>Discussion: </strong>The results indicate that GLP-1 RAs potentiate the antitumor effect of RT in breast cancer, primarily through modulation of apoptosis and the tumor microenvironment.</p><p><strong>Conclusion: </strong>GLP-1 RAs may be effective adjuvants to RT in breast cancer, particularly for patients with diabetes. The dual benefit of tumor sensitization and protection of normal tissues offers a promising therapeutic avenue.</p>","PeriodicalId":10991,"journal":{"name":"Current radiopharmaceuticals","volume":" ","pages":"318-332"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Nuclear Nanomedicines: Utilization of Radiolabelling Strategies, Drug Formulation, Delivery, and Regulatory Aspects for Disease Management.","authors":"Neeraj Gupta, Kalpana Nagpal","doi":"10.2174/0118744710373025250423042401","DOIUrl":"10.2174/0118744710373025250423042401","url":null,"abstract":"<p><p>By integrating the sensitivity of nuclear medicine and the precision of nanotechnology, mankind can explore the very promising nuclear nanomedicine technology. Such integration enabled the imaging of biological processes at the molecular level which is a blessing to modern disease management. The present work is an effort to highlight the multifaceted applications of radiolabelled nanomaterials across various imaging modalities, formulation assessment, drug development, regulatory considerations, and therapeutic interventions. The present work highlights the application of radiolabelled nanomaterials for molecular imaging. The single-photon emission computed tomography (SPECT), positron emission tomography (PET); and hybrid multimodalities, along with their key features, are inherent parts of this discussion. The discussion continues with the assessment procedures of new formulations and their implications for drug delivery and the associated regulatory affairs. Cell tracking strategies that allow real-time monitoring of cellular behaviour <i>in vivo</i>; and radionuclide therapy with targeted and precise treatment are explained with the comparison of different strategies. This is followed by the explanation of how the drug delivery systems incorporating molecular imaging radiotracers enable tracking of <i>in vivo</i> drug behavior, further facilitating optimization of dosage forms and therapeutic efficacy. Thus, this manuscript provides a comprehensive overview of the utilization of radiolabelling strategies across the spectrum of drug formulation, delivery, and regulatory aspects, which is a way forward to future projections in nuclear nanomedicine. In conclusion, the emergence of nuclear nanomedicines is a disease management breakthrough in modern healthcare systems. This innovative approach not only provides tailored diagnostics but also offers innovative therapeutic solutions.</p>","PeriodicalId":10991,"journal":{"name":"Current radiopharmaceuticals","volume":" ","pages":"262-282"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"RNA Binding Proteins are Pivotal Regulators of Cancer Radioresistance and Potential Targets for Preventing Tumor Recurrence.","authors":"Vasanth Kanth Thasma LoganathBabu, Srisri Satishkartik, Vanshikaa Karthikeyan, Sayantani Chattopadhyay, Shriya P, Harin N Ganesh, Kirubakaran Rangasamy, Satish Ramalingam, ArulJothi Kandasamy Nagarajan","doi":"10.2174/0118744710366175250425101010","DOIUrl":"10.2174/0118744710366175250425101010","url":null,"abstract":"<p><p>RNA-binding proteins (RBPs) regulate gene expression at the post-transcriptional level and are important factors in cancer progression and response to various therapeutic strategies. Radioresistance, an obstacle caused due to various intrinsic and extrinsic factors, remains a major hindrance in the treatment of cancer and could lead to tumor recurrence. Though research is being conducted on the cause and association of radioresistance with various cellular and environmental factors, there remains much to be explored and discovered. The roles of several RNA-binding proteins in tumor progression and metastasis are well documented. In addition, recent studies suggest the connection between Cancer Stem Cells (CSCs) and chemoresistance. We and others have extensively studied the regulatory role of RBPs in regulating CSCs. Resistance to radiation therapy and the involvement of RBPs in this process is under-studied. In this review, we have provided an updated compilation of the significant role played by RBPs in radioresistance.</p>","PeriodicalId":10991,"journal":{"name":"Current radiopharmaceuticals","volume":" ","pages":"245-261"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143987151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Daniel M Machado, Daniel A Bulzico, Lidia F Fontes, Rossana C R de Mello, Simone Basso Locatelli, Priscilla B Pujatti
{"title":"Real-world Data on Intermediate-risk Differentiated Thyroid Cancer Biochemical Response to 3700 or 5550 MBq of [<sup>131</sup>I]Sodium Iodide.","authors":"Daniel M Machado, Daniel A Bulzico, Lidia F Fontes, Rossana C R de Mello, Simone Basso Locatelli, Priscilla B Pujatti","doi":"10.2174/0118744710374569250415095218","DOIUrl":"10.2174/0118744710374569250415095218","url":null,"abstract":"<p><strong>Introduction: </strong>The ideal [<sup>131</sup>I]Sodium Iodide activity for intermediate-risk thyroid cancer treatment is still uncertain. The objective of this study is to compare the biochemical responses to radioiodine therapy (RIT) of intermediate-risk thyroid cancer patients administered [<sup>131</sup>I]Sodium Iodide at doses of 3700 MBq (100 mCi) and 5550 MBq (150 mCi).</p><p><strong>Methods: </strong>A retrospective study was conducted by reviewing the medical records of intermediaterisk thyroid cancer patients who received RIT between 2016 and 2020 at a reference cancer hospital in Brazil. Sociodemographic and clinical data were evaluated at the time of diagnosis. Clinical data during two years of follow-up were reviewed, and biochemical responses were determined according to the American Thyroid Association (ATA, 2015 version). Responses to doses of 3700 MBq (100 mCi) and 5550 MBq (150 mCi) of [<sup>131</sup>I]Sodium Iodide were compared.</p><p><strong>Results: </strong>No significant statistical differences were observed concerning the biochemical therapeutic responses of patients treated with 3700 MBq or 5550 MBq (p = 0.088). The presence of nodal metastasis and positive pre-RIT thyroglobulin did not influence biochemical responses to radioiodine.</p><p><strong>Discussion: </strong>According to ATA 2015 guidelines, RIT may be administered to patients classified at intermediate risk for the ablation of post-surgical tissue remnants, as well as an adjuvant treatment for potential persistent tumor foci and to reduce recurrence risks. These recommendations, however, do not specify the appropriate radioiodine dosage and this has been a topic of extensive debate.</p><p><strong>Conclusion: </strong>Intermediate risk thyroid-cancer patients presented similar therapeutic responses to the doses of 3700 MBq and 5550 MBq [<sup>131</sup>I]Sodium Iodide.</p>","PeriodicalId":10991,"journal":{"name":"Current radiopharmaceuticals","volume":" ","pages":"293-301"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143967992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nedim C M Gulaldi, Nadide Basak Gulleroglu, Selma Cakmakci, Fatma Arzu Gortan, Neriman Sari
{"title":"Dilemma on Pancreatic Uncinate Process Uptake on Ga68-DOTA Peptide PET/CT in Pediatric Neuroblastoma: Physiologic or Metastases?","authors":"Nedim C M Gulaldi, Nadide Basak Gulleroglu, Selma Cakmakci, Fatma Arzu Gortan, Neriman Sari","doi":"10.2174/0118744710226018250206105536","DOIUrl":"10.2174/0118744710226018250206105536","url":null,"abstract":"<p><strong>Introduction: </strong>The Ga68-DOTATATE PET/CT scan is an alternative imaging modality for the follow-up of children with neuroblastoma when the I123-MIBG scan was negative or weak. Somatostatin receptors (SSR) can be expressed in neuroblastoma lesions, and when this happens, targeting these receptors may be a good alternative to treating this disease in addition to conventional treatments. Our aim is to focus on the interpretation of one of the physiological tracer uptake sites, the uncinate process of the pancreas, using DW-MRI scans.</p><p><strong>Methods: </strong>We present and discuss 4 cases with neuroblastoma for a technical note. Imaging scans for SSR were performed using Ga68-DOTATATE PET/CT, and all showed varying degrees of increased uptake at the uncinate process of the pancreas on PET/CT images. We also performed a DW-MRI study to distinguish physiologic uptake in this region of the pancreas from metastatic involvement.</p><p><strong>Results: </strong>Two of them showed diffusion restriction, with one of them also showing multiple masses within the liver. The other 2 children with high pancreatic uncinate process uptake did not exhibit any findings that indicated pancreatic involvement in the disease, based on DW-MRI images and clinical findings.</p><p><strong>Conclusion: </strong>We recommend comparing DW-MRI scans and SSR-PET/CT scans to determine the true state of physiologically elevated SSR concentration and consequently indicate increased uptake on the images. The radiotracer concentration at the high uptake site did not appear to correlate with malignant involvement of the organ. The higher number of patients may allow a statistical comparison of the tracer with malignancy status.</p>","PeriodicalId":10991,"journal":{"name":"Current radiopharmaceuticals","volume":" ","pages":"333-339"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Victoria Shestakova, Anna Smirnova, Anna Yakimova, Sergey Koryakin, Denis Baranovskii, Vyacheslav Saburov, Elena Yatsenko, Alexander Moiseev, Sergey Ivanov, Ekaterina Smirnova, Svetlana Belkina, Grigory Demyashkin, Lyudmila Komarova, Peter Shegay, Andrey Kaprin, Ilya Klabukov
{"title":"Biological Efficacy of Ionizing Radiation Sources on 3D Organotypic Tissue Slices Assessed by Fluorescence Microscopy.","authors":"Victoria Shestakova, Anna Smirnova, Anna Yakimova, Sergey Koryakin, Denis Baranovskii, Vyacheslav Saburov, Elena Yatsenko, Alexander Moiseev, Sergey Ivanov, Ekaterina Smirnova, Svetlana Belkina, Grigory Demyashkin, Lyudmila Komarova, Peter Shegay, Andrey Kaprin, Ilya Klabukov","doi":"10.2174/0118744710293570240419110322","DOIUrl":"10.2174/0118744710293570240419110322","url":null,"abstract":"<p><strong>Objective: </strong>Traditional cell-based radiobiological methods are inadequate for assessing the toxicity of ionizing radiation exposure in relation to the microstructure of the extracellular matrix. Organotypic tissue slices preserve the spatial organization observed <i>in vivo</i>, making the tissue easily accessible for visualization and staining. This study aims to explore the use of fluorescence microscopy of physiologically relevant 3D tissue cultures to assess the effects of ionizing radiation.</p><p><strong>Methods: </strong>Organotypic tissue slices were obtained by vibratome, and their mechanical properties were studied. Slices were exposed by two ionizing radiation sources; electron beams (80 Gy and 4 Gy), and soft gamma irradiation (80 Gy and 4 Gy). Two tissue culture protocols were used: the standard (37°C), and hypothermic (30°C) conditions. A qualitative analysis of cell viability in organotypic tissue slices was performed using fluorescent dyes and standard laser confocal microscopy.</p><p><strong>Results: </strong>Biological dosimetry is represented by differentially stained 200-μm thick organotypic tissue sections related to living and dead cells and cell metabolic activity.</p><p><strong>Conclusion: </strong>Our results underscore the ability of fluorescence laser scanning confocal microscopy to rapidly assess the radiobiological effects of ionizing radiation <i>in vitro</i> on 3D organotypic tissue slices.</p>","PeriodicalId":10991,"journal":{"name":"Current radiopharmaceuticals","volume":" ","pages":"64-72"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140862297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Left Ventricular Wall Motion as an Additional Valuable Parameter in Diabetic Patients with Normal Myocardial Perfusion Imaging.","authors":"Amirhesam Davari, Fatemeh Jalali-Zefrei, Bahare Gholami-Chabok, Shiva Tabaghi, Soghra Farzipour, Kourosh Delpasand, Seyed Mehdi Mousavi","doi":"10.2174/0118744710312688240814100448","DOIUrl":"10.2174/0118744710312688240814100448","url":null,"abstract":"<p><strong>Background: </strong>Gated SPECT is an established technique for assessment of left ventricular function in cardiovascular disease patients. However, there is little information about the influence of diabetes mellitus on gated SPECT parameters. This study was established to assess gated SPECT parameters in Diabetes Mellitus (DM) and non-diabetes mellitus (non-DM) patients with normal Myocardial Perfusion Imaging (MPI).</p><p><strong>Methods: </strong>In this analytical cross-sectional study, 314 patients (157 DM, 157 non-DM) with normal MPI were enrolled. Prevalence of risk factors for CAD like hypertension (HTN), and dyslipidemia were found to be significantly higher (p <0.01) in DM patients compared to non-DM.</p><p><strong>Results: </strong>No statistically significant difference was observed among the TID, ESV, EDV, PFR, TTPF, and Wall Thickness (WT) parameters between DM and non-DM patients. Wall motion (Wm) in DM patients was significantly higher compared to non-DM patients. (3.9 ± 0.51 vs. 2.69 ± 0.48 for DM and non-DM patients, respectively, p-value:0.01). Also, there was no significant difference in Wm in the two groups with and without HTN. This shows the independent effect of DM on the Wm.</p><p><strong>Conclusion: </strong>This study believes that the Wm parameter should be noted for the early diagnosis or prevention of heart disease in DM patients. These findings can indicate the gradual changes in the movements of the left ventricle and the beginning of the progression of diabetic cardiomyopathy.</p>","PeriodicalId":10991,"journal":{"name":"Current radiopharmaceuticals","volume":" ","pages":"141-146"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ensiyeh Bahadoran, Yazdan Zafari, Ali Homaei, Manijeh Jalilvand, Sahar Moghbelinejad
{"title":"Role of the p53/miR-34a/SIRT1 Feedback Loop in Metformin-induced Radiosensitivity of Colorectal Cancer Cells.","authors":"Ensiyeh Bahadoran, Yazdan Zafari, Ali Homaei, Manijeh Jalilvand, Sahar Moghbelinejad","doi":"10.2174/0118744710331660250127115004","DOIUrl":"10.2174/0118744710331660250127115004","url":null,"abstract":"<p><strong>Introduction: </strong>Metformin induces radiation sensitivity in cancer cells, including colorectal cancer cells; however, the exact molecular mechanisms underlying its radiosensitive effects are not yet known. In this study, we investigated the role of the p53/miR-34a/SIRT1 pathway in the radiosensitivity of colon cancer cells.</p><p><strong>Methods: </strong>The study was carried out from 2020 to 2022 at the Qazvin University of Medical Science's Cellular and Molecular Research Center. Two colorectal cancer cell lines (SW480 and SW620) obtained from primary and secondary tumors derived from a single patient were used as the study samples. After subjecting the cells to 50 Gy of radiation, we generated radioresistant cell lines. Resistant cells were treated with 50 μM metformin. Metformin-treated and untreated resistant cells constituted the study groups. The expression levels of miR-34-a and Sirtunin1 (SIRT1) were evaluated using Quantitative Real-time PCR. The rates of cell proliferation and apoptosis were assessed using a Cell Counting Kit-8 (CCK-8) assay and flow cytometry. Western blot analysis was performed to quantify the expression of proteins. For statistical analysis, the Student's ttest was carried out to examine the mean differences between the two groups, and analysis of variance (ANOVA) was used to examine additional groups.</p><p><strong>Results: </strong>Our results showed that the expression of miR-34-a was downregulated (0.29 ± 0.11) in radiation-resistant cancer cells (P <0.001), while the expression of SIRT-1 was upregulated (4.5 ± 0.25) (P <0.001). Metformin increased the radiosensitivity of colon cancer cells in a time- and dose-dependent manner. Treatment with 50 μM metformin after 48h caused decreased cell viability and increased apoptosis in resistant cells. We observed downregulation of SIRT-1 (1.1 ± 0.45) and upregulation of miR-34-a (4.3 ± 1.3) (P <0.001) in metformin-treated cells. In contrast, western blotting results showed the upregulation of acetylated P53 in metformin-treated cells. Metformin function was reversed by SIRT1 inhibitors or by transfection with miR-34-a overexpressing plasmids.</p><p><strong>Conclusion: </strong>Based on these results, one of the radiosensitivity mechanisms of metformin in colorectal cancer is the modulation of the p53/miR-34a/SIRT1 loop.</p>","PeriodicalId":10991,"journal":{"name":"Current radiopharmaceuticals","volume":" ","pages":"340-351"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}