Current molecular medicine最新文献

{"title":"Thymoquinone-PLGA-PF68 Nanoparticles Induce S Phase Cell Cycle Arrest and Apoptosis, Leading to the Inhibition of Migration and Colony Formation in Tamoxifen-Resistant Breast Cancer Cells.","authors":"Nurul Shahfiza Noor, Shahrul Bariyah Sahul Hamid","doi":"10.2174/0115665240347014241203065055","DOIUrl":"10.2174/0115665240347014241203065055","url":null,"abstract":"<p><strong>Background: </strong>A biocompatible polymeric nanoparticle, TQ-PLGA-PF68, was developed through the interaction of the phytochemical thymoquinone (TQ) encapsulated in poly(L-lactide-co-glycolide)-b-poly(ethylene glycol) (PLGA-PEG) with Pluronics F68. So far, this combination has not been assessed on breast cancer cells resistant to anti-cancer drugs. Therefore, this study aimed to assess the cell death caused by TQ-PLGA-PF68 nanoparticles, particularly in resistant breast cancer cell lines expressing estrogen receptor (ER) positivity, such as TamR MCF-7.</p><p><strong>Methods: </strong>The antiproliferative activity of TQ-PLGA-PF68 nanoparticles was measured using the MTS assay. The cytotoxic effects were further evaluated through colony formation assay and scratch-wound healing assay. Terminal deoxynucleotidyl transferase dUTP Nick End Labeling (TUNEL) assay was performed to determine the characteristics of the apoptosis as well as cell cycle arrest induced by TQ-PLGA-PF68 nanoparticles. The localization of these nanoparticles in the cells was examined using Transmission Electron Microscopy (TEM).</p><p><strong>Results: </strong>With a TQ concentration of 58.5 μM encapsulated within the nanoparticles, cytotoxicity analysis revealed a significant inhibition of cell proliferation (p<0.05). This finding was corroborated by the results of the colony formation assay. Treatment with TQ-PLGA-PF68 nanoparticles significantly decreased the number of surviving TamR MCF-7 cells by 35% (p<0.001) compared to untreated TamR MCF-7 cells. Concurrently, the scratch-wound healing assay indicated a closure rate of 50% versus >80% (p<0.05) in untreated TamR MCF-7 cells at 12 hours post-wounding. The TUNEL assay successfully confirmed the apoptosis characteristics associated with cell cycle arrest. TEM observation confirmed the cellular internalization of these nanoparticles, suggesting the in vitro therapeutic potential of the formulation.</p><p><strong>Conclusion: </strong>In this study, a significant functional change in TamR MCF-7 cells induced by the TQ nanoparticles was observed. The unique incorporation of TQ into the PLGA-PEG and Pluronics F68 formulation preserved its bioactivity, thereby reducing the migratory and proliferative traits of drug-resistant cells. This discovery may pave the way for exploring the application of biocompatible polymeric TQ nanoparticles as a novel therapeutic approach in future studies pertaining to resistant breast cancer.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":"760-772"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001695","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":"From Reactive Hyperplasia to Neoplastic Changes: Histopathological Insights into Lymphadenopathy.","authors":"Nehad Khan, Farah Fatima Abbas, Saba Kamil, Ruqaiya Shahid, Syeda Tahiya Shah, Alina Rizvi, Noor Kamil, Raahim Ali","doi":"10.2174/0115665240361964241219045031","DOIUrl":"10.2174/0115665240361964241219045031","url":null,"abstract":"<p><strong>Background: </strong>Inflammation, infection, autoimmune diseases, or malignancy can cause the abnormal proliferation of lymphocytes; therefore, clinicians should always take detailed history and physical examination to screen the patient for lymphadenopathy.</p><p><strong>Objectives: </strong>The aim and objective of the current study was to assess the pattern of diseases causing lymphadenopathies in the Pakistani Population.</p><p><strong>Methodology: </strong>The current study was a cross-sectional study. Data were obtained from existing patient records from Dow Diagnostic Research and Reference Laboratory [DDRRL]-Dow University of Health Sciences [DUHS] from Jan 2020 to Dec 2022. Patients undergoing chemotherapy and biopsies with poor preservation and inconclusive diagnosis were excluded from the study, while patients of any age, gender, and various sites of lymphadenopathy were included in this study. Ethical approval was obtained from the ethical Review Board [IRB] of Dow University of Health Sciences [DUHS].</p><p><strong>Results: </strong>A total of 675 FNAC and lymph node biopsies of lymph nodes were obtained. Age, location, and gender were taken into consideration when analyzing the lymph node biopsy materials of these patients. There were 200 [29.62%] males and 475 [70.37%] females. The age range of the patients was 1 year to 80 years, and the mean [SD] age of the patients was 33.76 ± 17.54 years.</p><p><strong>Conclusion: </strong>In the current study, we aim to provide guidance to the clinician on initial diagnostic laboratory testing, imaging, and the potential need for biopsy by evaluating the pattern of diseases causing lymphadenopathy in our population.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":"773-778"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482471","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":"Limning of HIF-2 and HIF-3 in the Tumor Microenvironment: Developing Concepts for the Treatment of Hypoxic Cancer.","authors":"Suman Kumar Ray, Sukhes Mukherjee","doi":"10.2174/0115665240303179240427071748","DOIUrl":"10.2174/0115665240303179240427071748","url":null,"abstract":"<p><p>Hypoxia, characterized by insufficient oxygen supply to tissues, is a significant factor in tumor growth and resistance to treatment. The hypoxia-inducible factor (HIF) signaling pathway is activated when oxygen levels decline, influencing cell activities and promoting tumor progression. HIF-1α and HIF-2α are the main targets for therapeutic intervention in tumors. Nevertheless, the significance of HIF-2α is often overlooked. This review examines the physiological role of HIF-2α in tumor growth and its involvement in tumor growth. HIFs, composed of hypoxia-responsive α and oxygeninsensitive β subunits, play a crucial role in controlling gene expression in both normal and solid tumor tissues under low oxygen levels. HIF-3α, formerly considered a detrimental modulator of HIF-regulated genes, exerts a transcriptional regulatory role by inhibiting gene expression through competition with HIF-1α and HIF-2α for binding to transcriptional sites in target genes under hypoxia. Recent research indicates that various HIF-3 variants exhibit distinct and potentially contrasting functionalities. Hypoxia often occurs during the initiation and progression of cancer formation. Recent research has discovered that HIF-2α, also known as endothelial PAS domain protein 1, has a significant impact on tumors. HIF-2α is a significant cancer-causing gene and a crucial predictor of prognosis in non-small cell lung cancer. However, due to limited research investigating the relationship between HIF-2α and small-cell lung cancer, it is not possible to reach a definitive conclusion. HIF-2α plays a vital function in cancer by preserving the stemness of cancer cells. This review provides a comprehensive overview of HIF-2 and the role of HIF-3 in various cancer-related processes, as well as its potential as a targeted therapeutic approach.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":"513-521"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141064281","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":"Targeting Ubiquitin-specific Protease 5 Overcomes Chemoresistance via Negatively Regulating p53 in Gastric Cancer.","authors":"Jing Song, Lei Liu, Fang Wang, Di Bao","doi":"10.2174/0115665240278762240202103722","DOIUrl":"10.2174/0115665240278762240202103722","url":null,"abstract":"<p><strong>Background: </strong>Resistance to chemotherapy is a major obstacle in the clinical management of gastric cancer, and the mechanisms underlying chemoresistance remain largely unknown.</p><p><strong>Aims: </strong>This study aimed to investigate the involvement of ubiquitin-specific protease 5 (USP5), a deubiquitinating enzyme, in gastric cancer chemoresistance.</p><p><strong>Methods: </strong>USP5 expression was analyzed in fifty paired gastric cancer and adjacent normal tissues, chemo-sensitive and chemo-resistant gastric cancer lines using quantitative ELISA. The role of USP5 was determined using loss-of-function and gainof- function methods. USP5-mediated downstream effectors were analyzed using biochemical methods focusing on p53.</p><p><strong>Results: </strong>USP5 expression was comparable in tumors and normal in the majority of the cohort. Following chemotherapy treatment, USP5 expression significantly increased in gastric cancer cells, while p53 levels remained unaltered. Overexpression of USP5 amplified growth and migration while decreasing apoptosis induced by serum withdrawal across multiple gastric cancer cell lines. Conversely, USP5 knockdown effectively heightened gastric cancer sensitivity to paclitaxel and 5-FU treatments, particularly targeting chemo-resistant gastric cancer cells by inhibiting proliferation and migration and inducing apoptosis. Additionally, USP5 knockdown increased levels of p53 but not MDM2, increased p53 activity and increased transcription of p53 target genes. In contrast, USP5 overexpression decreased the level and activity of p53 and inhibited transcription of p53 target genes. The anti-proliferative, anti-migratory, and pro-apoptotic effects of USP5 were significantly diminished upon p53 depletion, highlighting the interplay between p53 and USP5 in regulating gastric cancer cell activities. Additionally, USP5 inhibition suppressed chemo-resistant gastric cancer cell migration via suppressing epithelial-mesenchymal transition (EMT) and RhoA activity.</p><p><strong>Conclusion: </strong>Targeting USP5 inhibition has emerged as a promising alternative therapeutic approach to overcoming chemoresistance in gastric cancer. Additionally, our study sheds light on the novel role of USP5 as a regulator of p53 in gastric cancer.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":"211-221"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139722003","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":"Metabolic Derangement in Non-Alcoholic Fatty Liver Disease: Opportunities for Early Diagnostic and Prognostic Markers.","authors":"Abhinav Verma, Mittal Rishabh, Navaneethakannan Mathiyazhagan, Sonu Singh Ahirwar, Sukhes Mukherjee, Ashwin Kotnis","doi":"10.2174/0115665240269082240213115711","DOIUrl":"10.2174/0115665240269082240213115711","url":null,"abstract":"<p><p>Non-alcoholic fatty liver disease is a globally prevalent disorder that can rapidly progress if not detected early. Currently, no accepted markers exist for early diagnosis and prognosis of NAFLD. This review describes derangement in major metabolic pathways of lipid, carbohydrate, and amino acids in NAFLD. It suggests that measuring levels of thrombospondin, TyG index, asymmetric dimethylarginine, LAL-A, GLP-1, FGF-21, and GSG index are potential markers for early diagnosis of NAFLD. A single marker may not indicate early NAFLD, and further large-scale studies on correlating levels of Thrombospondin-2, triglyceride-glucose index, and FGF-21 with NAFLD are warranted.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":"269-277"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139971302","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":"Advances in Monoclonal Antibody Therapies for Triple-Negative Breast Cancer: Immunotherapeutic and Targeted Strategies.","authors":"Amirreza Khalaji, Sara Hadad, Amirreza Jabbaripour Sarmadian, Fatemeh Ojaghlou, Elham Mohebi Janagard, Behzad Baradaran","doi":"10.2174/0115665240287767240115062343","DOIUrl":"10.2174/0115665240287767240115062343","url":null,"abstract":"<p><p>Triple-negative breast cancer (TNBC) presents considerable obstacles because of its highly aggressive characteristics and limited availability of specific therapeutic interventions. The utilization of monoclonal antibody (mAb)-based immunotherapy is a viable approach to tackle these difficulties. This review aims to examine the present state of mAb-based immunotherapy in TNBC, focusing on the underlying mechanisms of action, clinical applications, and existing challenges. The effectiveness of mAbs in reducing tumor development, regulating immune responses, and changing the tumor microenvironment has been demonstrated in many clinical investigations. The challenges encompass several aspects such as the discovery of biomarkers, understanding resistance mechanisms, managing toxicity, considering costs, and ensuring accessibility. The future is poised to bring forth significant advancements in the field of biomedicine, particularly in the areas of new mAbs, personalized medicine, and precision immunotherapy. In conclusion, mAb-based immunotherapy has promise in revolutionizing the treatment of TNBC, hence providing a possible avenue for enhanced patient outcomes and quality of life.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":"445-459"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139575542","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":"Morphine-Induced Elevation of Reactive Oxygen Species Attenuates Chemotherapy Efficacy in Diverse Cancer Cell Types.","authors":"Gong Chen, Si Zeng, Bin Wang, Daguo Wang, Jie Ding, Tao Feng","doi":"10.2174/0115665240314564241129044548","DOIUrl":"10.2174/0115665240314564241129044548","url":null,"abstract":"<p><strong>Background: </strong>Morphine, a mu-opioid receptor (MOR) agonist commonly utilized in clinical settings alongside chemotherapy to manage chronic pain in cancer patients, has exhibited contradictory effects on cancer, displaying specificity toward certain cancer types and doses.</p><p><strong>Objective: </strong>The aim of this study was to conduct a systematic assessment and comparison of the impacts of morphine on three distinct cancer models in a preclinical setting.</p><p><strong>Methods: </strong>Viability and apoptosis assays were conducted on a panel of cancer cell lines following treatment with morphine, chemotherapy drugs alone, or their combination. Oxidative stress levels, along with the activities of superoxide dismutase and catalase, were measured. Rescue studies were also carried out using antioxidant reagents.</p><p><strong>Results: </strong>Morphine induces resistance to conventional chemotherapeutic agents. It was observed that while morphine affected cell viability differently among ovarian cancer, anaplastic thyroid cancer, and oral squamous cell carcinoma, at concentrations that did not directly impact cancer cell viability, it significantly mitigated the inhibitory effects of chemotherapeutic agents across all tested cancer cells. This phenomenon persisted irrespective of the chemotherapeutic agent used, including cisplatin, doxorubicin, and 5-FU. It remained unaffected by adding naloxone, the MOR receptor antagonist, indicating that morphine's mechanism is independent of the μ- opioid receptor. Moreover, it was demonstrated that morphine heightened cellular reactive oxygen species (ROS) levels and suppressed the activities of superoxide dismutase and catalase. Rescue studies revealed that the addition of antioxidant reversed the protective impact of morphine on cancer cells against chemotherapy.</p><p><strong>Conclusion: </strong>These findings hold promise in potentially guiding the clinical application of morphine for cancer patients undergoing chemotherapy.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":"460-471"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001684","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":"Ribosomal DNA and Neurological Disorders.","authors":"Hong Zhou, Yuqing Xia, Rui Zhu, Yuemei Zhang, Xinming Zhang, Yongjian Zhang, Jun Wang","doi":"10.2174/0115665240292079240513093708","DOIUrl":"10.2174/0115665240292079240513093708","url":null,"abstract":"<p><p>Ribosomal DNA (rDNA) is important in the nucleolus and nuclear organization of human cells. Defective rDNA repeat maintenance has been reported to be closely associated with neurological disorders, such as Alzheimer's disease, Huntington's disease, Parkinson's disease, amyotrophic lateral sclerosis, frontotemporal dementia, depression, suicide, etc. However, there has not been a comprehensive review on the role of rDNA in these disorders. In this review, we have summarized the role of rDNA in major neurological disorders to sort out the correlation between rDNA and neurological diseases and provided insights for therapy with rDNA as a target.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":"556-566"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141080772","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":"The Protective Role of miR-125b in Hepatocellular Carcinoma: Unraveling Tumor-Suppressive Mechanisms.","authors":"Mahrokh Abouali Gale Dari, Vahid Vahedian, Bartosz Kempisty, Olanrewaju B Morenikeji, Maryam Farzaneh, Amir Anbiyaiee","doi":"10.2174/0115665240304247240529074123","DOIUrl":"10.2174/0115665240304247240529074123","url":null,"abstract":"<p><p>MicroRNAs (miRNAs) have emerged as crucial regulators of gene expression, playing pivotal roles in various biological processes, including cancer development and progression. Among them, miR-125b has garnered significant attention due to its multifaceted functional roles in human hepatocellular carcinoma (HCC). Extensive research has revealed that miR-125b plays a dual role in HCC, acting as both a tumor suppressor and an oncogene, depending on the context. As a tumor suppressor, miR-125b inhibits HCC by targeting key oncogenic pathways and genes involved in cell proliferation, migration, invasion, and angiogenesis. Its downregulation in HCC is frequently observed and correlates with aggressive tumor characteristics and poor prognosis. Conversely, miR-125b can also function as an oncogene in specific HCC subtypes or under certain conditions. It has been shown to promote HCC growth, metastasis, and therapeutic resistance by targeting tumor suppressor genes, modulating the epithelial-mesenchymal transition (EMT) process, and enhancing cancer stem cell-like properties. The upregulation of miR-125b in HCC has been associated with advanced disease stages and unfavorable clinical outcomes. Furthermore, a complex network of regulatory mechanisms influences the dysregulation of miR-125b expression in HCC. Understanding these regulatory mechanisms is crucial for deciphering the precise functional roles of miR-125b in HCC and exploring its potential as a diagnostic biomarker or therapeutic target. In the current review study, we comprehensively elucidated the diverse functional roles of miR-125b in HCC, providing a comprehensive overview of its regulatory mechanisms and impact on key cellular processes involved in HCC progression.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":"663-671"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141300287","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":"Study on the Mechanism of Notch Pathway Mediates the Role of Lenvatinib-resistant Hepatocellular Carcinoma Based on Organoids.","authors":"Weiqing Feng, Haixiong Zhang, Qing Yu, Hao Yin, Xiaowei Ou, Jie Yuan, Liang Peng","doi":"10.2174/0115665240268201231213095302","DOIUrl":"10.2174/0115665240268201231213095302","url":null,"abstract":"<p><strong>Background: </strong>The emergence of treatment resistance has hindered the efficacy of targeted therapies used to treat patients with hepatocellular carcinoma (HCC).</p><p><strong>Objective: </strong>This study aimed to explore the mechanism of organoids constructed from lenvatinib-resistant HCC cells.</p><p><strong>Methods: </strong>Hep3B cell and human HCC organoids were cultured and identified using hematoxylin and eosin staining and Immunohistochemistry. Lenvatinib-sensitive/ resistant Hep3B cells were constructed using lenvatinib (0, 0.1, 1, and 10 μM) and lenvatinib (0, 1, 10, and 100 μM). qRT-PCR and flow cytometry were utilized to determine HCC stem cell markers CD44, CD90, and CD133 expressions. Transcriptome sequencing was performed on organoids. Western blot evaluated Notch pathwayrelated proteins (NOTCH1 and Jagged) expressions. Furthermore, DAPT, an inhibitor of the Notch pathway, was used to investigate the effects of lenvatinib on resistance or stemness in organoids and human HCC tissues.</p><p><strong>Results: </strong>The organoids were successfully cultivated. With the increase of lenvatinib concentration, sensitive cell organoids were markedly degraded and ATP activity was gradually decreased, while there was no significant change in ATP activity of resistant cell organoids. CD44 expressions were elevated after lenvatinib treatment compared with the control group. KEGG showed that lenvatinib treatment of organoids constructed from Hep3B cells mainly activated the Notch pathway. Compared with the control group, NOTCH1 and Jagged expressions elevated, and ATP activity decreased after lenvatinib treatment. However, ATP activity was notably decreased after DAPT treatment. Moreover, DAPT inhibited lenvatinib resistance and the increase in the expressions of CD44 caused by lenvatinib. Besides, 100 μM lenvatinib significantly inhibited the growth and ATP activity of human HCC organoids, and DAPT increased the inhibitory effect of lenvatinib.</p><p><strong>Conclusion: </strong>Lenvatinib regulated resistance and stemness in organoids via the Notch pathway.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":"343-352"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139424414","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}