{"title":"Expression of Elastin, F-Box and WD-40 Domain-Containing Protein 2, Fibrillin-1, and Alpha-Smooth Muscle Actin in Utilized Blood Vessels for explant culture-A New 3D in Vitro Vascular Model from Bovine Legs.","authors":"Mari Akiyama","doi":"10.1007/s12013-024-01647-5","DOIUrl":"10.1007/s12013-024-01647-5","url":null,"abstract":"<p><p>Elastic fibers of the internal and external elastic laminae maintain blood vessel shapes. Impairment of smooth muscle cell function leads to vascular disease development. F-box and WD-40 domain-containing protein 2 (FBXW2) is associated with elastic fibers and osteocalcin expression for bone regeneration in the periosteum. Here, it is hypothesized that FBXW2 has different roles in periosteum and blood vessels. Furthermore, if FBXW2 would be a component of elastic fiber of blood vessels, FBXW2 would be expressed where the well-known components elastin and fibrillin-1 are expressed. For this purpose, explant culture of blood vessels from bovine legs were performed for 5 weeks. It was found that elastin and FBXW2 were expressed within the elastic laminae, whereas fibrillin-1 was expressed around them. After explant culture, elastin and FBXW2 sustained the shape of the elastic fibers in the elastic lamina, whereas the fibrillin-1-rich layer became wide range and encompass toward intima and adventitia layers. Hematoxylin Eosin staining and immunohistochemistry of alpha-smooth muscle actin (α-SMA) revealed weakened media layer after 5 weeks culture. Although fibrillin-1 is a well-known component of elastic fibers and elastin, this study revealed that the location of fibrillin-1 is different from that of elastin, whereas FBXW2 is present in the same region as elastin from day 0 to week 5. In blood vessels, fibrillin-1 fibers around the elastic lamina may be oxytalan fibers. Thus, the proposed 3D in vitro model in this study is useful for identifying the mechanisms of vascular degradation.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":"2365-2378"},"PeriodicalIF":1.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12089167/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142890908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mechanistic Insights into Silymarin-Induced Apoptosis and Growth Inhibition in SPC212 Human Mesothelioma Cells.","authors":"Özlem Tomsuk, Sedat Kaçar","doi":"10.1007/s12013-024-01650-w","DOIUrl":"10.1007/s12013-024-01650-w","url":null,"abstract":"<p><p>Silymarin, a flavonoid complex isolated from Silybum marianum, possesses various biological properties, including antioxidant, anti-inflammatory, anti-glycation, and hepatoprotective effects. In the present study, we investigated the effects of silymarin on the SPC212 human mesothelioma cell line. MTT and neutral red assays were performed to examine the cytotoxic effects of silymarin. The apoptotic effect was investigated using AO/EB and DAPI staining, and morphological changes were observed using H&E and May-Grünwald staining. Additionally, immunocytochemistry was performed to detect Bax, Bcl2, and PCNA. Our results indicated that silymarin has a dose-dependent cytotoxic effect on SPC212 cells, with an IC<sub>50</sub> value of approximately 187.5 µM. Silymarin induces apoptotic hallmarks such as apoptotic bodies, cell shrinkage, and nuclear condensation. In conclusion, silymarin demonstrated cytotoxic and apoptotic effects as well as morphological changes in SPC212 human mesothelioma cells. Further detailed studies are warranted to explore the potential of silymarin as an anti-cancer agent.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":"2405-2414"},"PeriodicalIF":1.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142919009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Silencing of FZD7 Inhibits Endometriotic Cell Viability, Migration, and Angiogenesis by Promoting Ferroptosis.","authors":"Yi Zhang, Huifen Yang","doi":"10.1007/s12013-024-01656-4","DOIUrl":"10.1007/s12013-024-01656-4","url":null,"abstract":"<p><strong>Background: </strong>Endometriosis (EMS) is a difficult gynecological disease to cure. Frizzled-7 (FZD7) has been shown to be associated with the development of EMS, but its specific mechanism remains unclarified. This study aims to explore the role of FZD7 in EMS.</p><p><strong>Methods: </strong>RT-qPCR and western blot were used to detect the expression level of FZD7 in human endometrial stromal cells (hESCs) and human ectopic endometrial stromal cell line hEM15A. The interfering plasmid of FZD7 was established. CCK-8, EdU, wound healing, transwell invasion, and cytoskeletal staining assays were applied to evaluate the role of FZD7 silencing in hEM15A cell proliferation, invasion, and migration. Tube forming ability of cells was evaluated by tube formation assay. Cellular VEGF, GSH, and MDA levels were measure by kits. Intracellular lipid ROS and Fe<sup>2+</sup> levels were tested using C11-BODIPY (581/591) and FeRhoNox-1 probes, respectively. The ferroptosis-related protein SLC7A11, GPX4, and ACSL4 expressions were analyzed using western blot. The effects of ferroptosis on endometriotic cell viability, migration, and angiogenesis were further analyzed with the addition of an ferroptosis inhibitor (Fer-1).</p><p><strong>Results: </strong>FZD7 was upregulated in hEM15A cells, and silencing of FZD7 inhibited cell proliferation, migration, invasion, and angiogenesis abilities. Downregulation of FZD7 decreased cellular GSH level and elevated MDA level. Knockdown of FZD7 also caused an increase in intracellular ROS and Fe<sup>2+</sup> levels, as well as the downregulation of SLC7A11 and GPX4 levels and the upregulation of ACSL4 level, which are hallmarks of ferroptosis. However, the inhibitory effects of FZD7 knockdown on hEM15A cell progression were reversed when ferroptosis inhibitor Fer-1 added.</p><p><strong>Conclusion: </strong>The above indices suggest that FZD7 knockdown regulates endometriotic cell proliferation, invasion, migration, and angiogenesis via ferroptosis.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":"2471-2480"},"PeriodicalIF":1.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142963501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A Novel Hypoxia-Featured Genes Prognostic Model for Identification of Hypoxia Subtypes in Diffuse Large B-Cell Lymphoma.","authors":"Geng Lyu, Ruixin Sun, Xiaxin Liu, Zizhen Xu","doi":"10.1007/s12013-024-01637-7","DOIUrl":"10.1007/s12013-024-01637-7","url":null,"abstract":"<p><p>Diffuse large B-cell lymphoma (DLBCL), known as the predominant type of aggressive B-cell lymphoma, is biologically and clinically heterogeneous. The prognosis of DLBCL is quite different among subtypes. Hypoxia is one of the key elements in tumor microenvironment, promoting tumor progression by means of various mechanisms, such as increased proliferation, altered metabolism, enhanced angiogenesis, and greater migratory capability, among others. The primary purpose of this research is to investigate the connection between hypoxia-featured genes (HFGs), prognosis in DLBCL, and their capacity association with the immune microenvironment. Various hypoxia-associated patterns for DLBCL patients from GEO and TCGA databases were identified by means of an unsupervised consensus clustering algorithm. CIBERSORT and IOBR package is used to identify different immune infiltration status. To develop a predictive model using hypoxia-related genes, we conducted univariate Cox regression, multivariate Cox regression, and LASSO regression assessment. Subsequently, we confirmed the predictive importance of these hypoxia-associated genes, highlighting hypoxia-associated characteristics, and explored the connection between the hypoxia model and the immune environment. Three hypoxia clusters were identified. We also observed that each pattern of hypoxia response was significantly related to different prognoses. It was found that the immune status among hypoxia clusters is different. After developing a prognostic risk model using 5 hypoxia-related genes, we discovered that the risk score is related to immune factors and how effective drugs are in treating DLBCL. In DLBCL patients, varying hypoxia patterns correlate with both prognostic outcomes and the immune microenvironment. Hypoxia-featured genes (HFGs) function as a standalone predictive element in these patients. It is also potentially a reliable indicator for predicting clinical responses to ICI therapy and traditional drugs.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":"2265-2279"},"PeriodicalIF":1.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142811774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Caffeic Acid Phenethyl Ester Enhances Bone Repair-related Factors in MC3T3-E1 Cells.","authors":"Hitomi Kuramoto, Tadashi Nakanishi, Hiromichi Yumoto, Daisuke Takegawa, Katsuhiro Mieda, Keiichi Hosaka","doi":"10.1007/s12013-024-01644-8","DOIUrl":"10.1007/s12013-024-01644-8","url":null,"abstract":"<p><p>Apical periodontitis is an inflammatory disease caused by bacterial infection in the root canal that spreads to the apical periodontal tissues, resulting in bone resorption around the root apex as the disease progresses. Vascular endothelial growth factor (VEGF), a growth factor involved in angiogenesis, plays an important role in bone remodeling. We reported that caffeic acid phenethyl ester (CAPE), a bioactive substance of propolis, induces VEGF in odontoblast-like cells and dental pulp cells. However, the effects of CAPE on bone tissues remain unclear. This study was aimed to investigate the effects of CAPE on MC3T3-E1 cells, mice preosteoblast line. As a result, CAPE up-regulated the production of VEGF and induced the phosphorylation of extracellular signal-regulated kinases (ERK), p38 mitogen-activated protein kinase (MAPK), and stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) in MC3T3-E1 cells. Furthermore, CAPE increased the expression of factors involved in osteoblast differentiation, runt-related transcription factor 2 (Runx2), Osterix, and Wnt5a/b in MC3T3-E1 cells. In this study, we show that CAPE could induce bone repair-related factors in MC3T3-E1 cells.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":"2323-2331"},"PeriodicalIF":1.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"IRF7 Activates LCN2 Transcription to Enhance LPS-Induced Acute Lung Injury by Inducing Macrophage Ferroptosis and M1 Polarization.","authors":"Yali Lv, Lefeng Zhang","doi":"10.1007/s12013-024-01651-9","DOIUrl":"10.1007/s12013-024-01651-9","url":null,"abstract":"<p><p>Acute lung injury (ALI), a severe pulmonary disorder that poses a significant threat to life, is closely associated with macrophage ferroptosis and polarization. Lipocalin 2 (LCN2) has been previously reported to be implicated in the pathogenesis of ALI. However, the specific role of LCN2 in macrophage ferroptosis and polarization remains undetermined. Lipopolysaccharide (LPS) was used to establish a mouse model of ALI and also to stimulate mouse RAW264.7 cells. H&E staining was used for histopathologic evaluation, and immunohistochemistry analysis was used to determine the 4-HNE-positive cells. The secretion levels of TNF-α, IL-6, and IL-1β were assessed by ELISA. Gene and protein expression assays were performed using quantitative PCR and immunoblotting. The levels of MDA, GSH, ROS, and lipid ROS were detected to evaluate the alteration in ferroptosis. CD86<sup>+</sup> and CD206<sup>+</sup> cells were quantified by flow cytometry. The relationship between LCN2 and interferon regulatory factor 7 (IRF7) was confirmed by chromatin immunoprecipitation (ChIP) and luciferase reporter assays. LCN2 expression was upregulated in the lungs of LPS-induced ALI mice and LPS-stimulated RAW264.7 cells. In LPS-induced ALI mice, the depletion of LCN2 alleviated lung injury and ferroptosis, and also inhibited inflammation and macrophage M1 polarization. In LPS-stimulated RAW264.7 cells, the depletion of LCN2 suppressed ferroptosis, inflammation, and M1 polarization. Mechanistically, IRF7 enhanced LCN2 transcription in RAW264.7 cells by binding to its promoter region. More importantly, the silencing of IRF7 inhibited ferroptosis and M1 polarization in LPS-stimulated RAW264.7 cells by downregulating LCN2. Taken together, the IRF7/LCN2 cascade enhances the ferroptosis and M1 polarization of LPS-stimulated macrophages, thereby exacerbating ALI. Anti-IRF7 and anti-LCN2 therapies might potentially be exploited for the prevention and treatment in ALI.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":"2415-2430"},"PeriodicalIF":1.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142908880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Water-Soluble Ginseng Oligosaccharides Prevent Scopolamine-Induced Cholinergic Dysfunction and Inflammatory Cytokine Overexpression.","authors":"Ting Zeng, Chengwei Zhang, Lili Sun, Haiyan Xu","doi":"10.1007/s12013-024-01660-8","DOIUrl":"10.1007/s12013-024-01660-8","url":null,"abstract":"<p><p>Cholinergic deficiency and neuroinflammation are the two main factors of Alzheimer's disease. Recent studies have shown that water-soluble ginseng oligosaccharides (WGOS) derived from Panax ginseng roots can protect against scopolamine-induced impairments in learning and memory. However, the fundamental mechanisms remain unclear for the most part. The purpose of this study was to examine the effect of WGOS on cholinergic function and protein levels of proinflammatory cytokines in the hippocampus of mice. Mice were first pretreated with WGOS or saline, and then treated with scopolamine to establish an Alzheimer's disease model. The cognition memory of the mice was assessed through the behavioral test. The effect of WGOS on the cholinergic system was evaluated by measuring acetylcholine (ACh) neurotransmitter concentration and acetylcholinesterase (AChE) activity in the hippocampus. Using ELISA, the inflammatory cytokines IL-1β and TNF-α in the hippocampus were identified. This study found that WGOS treatment prevented the scopolamine-induced impairment of mice's recognition memory, as seen by their enhanced object recognition. In addition, WGOS prevented the scopolamine-induced decrease in ACh concentration and increase in AChE activity. Moreover, WGOS treatment inhibited scopolamine-induced upregulation of the inflammatory proteins IL-1β and TNF-α. These findings suggest that the amelioration of scopolamine-induced cognitive impairment in mice by WGOS was a consequence of the control of cholinergic function and inflammatory response in the hippocampus. Our findings suggest that WGOS should be investigated as a dietary supplement or medication for the treatment of learning and memory disorders in humans.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":"2511-2518"},"PeriodicalIF":1.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142919025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"miR-145b/AP2B1 Axis Contributes to Noise-induced Sensorineural Hearing Loss In a Male Mouse Model.","authors":"Xiang Gu, Mengxian Jiang, Wei Chen","doi":"10.1007/s12013-024-01665-3","DOIUrl":"10.1007/s12013-024-01665-3","url":null,"abstract":"<p><p>Sensorineural hearing loss (SNHL) is an increasingly prevalent sensory disorder, but the underlying mechanisms remain poorly understood. Adaptor related protein complex 2 subunit beta 1 (AP2B1) has been indicated to be detectable in mature cochleae. Nonetheless, it is unclear whether AP2B1 is implicated in the progression of SNHL. Male CBA/J mice were exposed to 2-20 kHz broadband noise at 96 or 101 dB SPL to induce temporary or permanent threshold shifts (TTS or PTS). Auditory brainstem responses were measured for hearing loss evaluation. Bioinformatics analysis was used to predict the upstream miRNAs of Ap2b1. RT-qPCR and western blotting were utilized to determine miR-145b and AP2B1 expression in mouse cochleae. Luciferase reporter assay was implemented to verify the interaction between Ap2b1 and miR-145b. Bioinformatics analysis identified miR-145b as an upstream miRNA of Ap2b1. AP2B1 expression was decreased and miR-145b expression was increased in mouse cochleae after PTS noise exposure. miR-145b targeted and negatively regulated Ap2b1 in PTS noise-exposed mice. Depletion of miR-145b alleviated auditory threshold shifts and outer hair cell loss in mice with exposure to PTS noise. In conclusion, inhibition of miR-145b ameliorates noise-induced SNHL in mice by upregulating AP2B1 expression.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":"2567-2575"},"PeriodicalIF":1.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"CAPRIN1 Transcriptionally Activated PLPP4 to Inhibit DOX Sensitivity and Promote Breast Cancer Progression.","authors":"Xiaorong Yuan, Xuejie Yang","doi":"10.1007/s12013-024-01614-0","DOIUrl":"10.1007/s12013-024-01614-0","url":null,"abstract":"<p><strong>Background: </strong>Phospholipid phosphatase 4 (PLPP4) has been identified as a potential regulator of cancer cell dynamics, however, the role of PLPP4 in breast cancer (BC) progression and the sensitivity of BC cells to doxorubicin (DOX) remain elusive.</p><p><strong>Methods: </strong>The study analyzed the expression of PLPP4 and cell cycle-associated protein 1 (CAPRIN1) expression in BC tissues and cells using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) and western blotting assays. Functional assays including colony formation, EdU, Transwell, and flow cytometry were employed to assess cellular behaviors. The sensitivity of BC cells to DOX was analyzed by CCK-8 assay and an in vivo xenograft model assay. The association between PLPP4 and CAPRIN1 was investigated using RNA immunoprecipitation assay and dual-luciferase reporter assay.</p><p><strong>Results: </strong>Upregulation of PLPP4 expression was observed in BC tissues and cells. Downregulation of PLPP4 expression in BC cells resulted in a suppression of their proliferative capacity, as well as a reduction in migratory and invasive capabilities. Additionally, this manipulation enhanced cell susceptibility to apoptosis and improved the sensitivity of these cells to DOX. When PLPP4 was knocked down in vivo in transplantable tumors, there was a marked enhancement in the responsiveness to DOX treatment. The transcription factor CAPRIN1 was found to regulate the expression of PLPP4 in the HCC1937 and MDA-MB-231 cell lines. Upregulation of CAPRIN1 was observed in both BC tissues and cells, and overexpression of PLPP4 reversed the effects of CAPRIN1 silencing on BC cell proliferation, migration, invasion, apoptosis, and DOX sensitivity.</p><p><strong>Conclusion: </strong>This study demonstrates that CAPRIN1 transcriptionally activates PLPP4 to inhibit DOX sensitivity and promote BC progression. Targeting PLPP4 may represent a novel therapeutic strategy to enhance the efficacy of DOX in BC patients.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":"2035-2045"},"PeriodicalIF":1.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Huicong Song, Xuefeng Sun, Xiaohua Wang, Tianhai Xie, Zhihui Zheng, Ying Ji, Yanyan Cui
{"title":"β-elemene Ameliorates Cisplatin Resistance of Gastric Cancer via Regulating Exosomal METTL3-m6A-ARF6 Axis.","authors":"Huicong Song, Xuefeng Sun, Xiaohua Wang, Tianhai Xie, Zhihui Zheng, Ying Ji, Yanyan Cui","doi":"10.1007/s12013-024-01615-z","DOIUrl":"10.1007/s12013-024-01615-z","url":null,"abstract":"<p><p>The medial overall survival is low in patients with gastric cancer (GC) at advanced stage, in which drug resistance plays an important role. β-elemene has been established as the suppressed role on GC cell proliferation, however, the concrete mechanism of it remains unclear in cisplatin (DDP)-resistance GC. Cell counting kit-8 (CCK8) assay was used to measure the half maximal inhibitory concentration (IC<sub>50</sub>) values of DDP in DDP-resistance GC cell lines. Cell apoptotic rates and invasive ability were tested by flow cytometry and transwell assay. Western blot and reverse-transcription quantitative polymerase chain reaction (RT-qPCR) were utilized to detect the protein and mRNA levels of methyltransferase like-3 (METTL3) and ADP ribosylation factor 6 (ARF6). SRAMP websites and methylated RNA immunoprecipitation (MeRIP) assay were applied to predicted m6A sites and verified m6A levels of ARF6 respectively. RNA immunoprecipitation (RIP) was used to explore the interaction between these two molecules. Xenograft tumor models were constructed to demonstrate the effects of β-elemene in vivo. β-elemene improved drug sensitivity and curbed malignant cell activities of DDP-resistance GC cells in vitro. ARF6 was upregulated in DDP-resistance GC cells and tissues, and its overexpression could abrogate the effects on DDP-resistant GC cells mediated by β-elemene treatment. Intracellular and exosomal METLL3 expression were elevated in and from DDP-resistance GC cell lines. Exosomal METTL3 released from DDP-resistance GC cells could counteract the effects of β-elemene on DDP-resistance GC cells partly via regulating ARF6 expression in the m6A-dependent manner. β-elemene could suppress DDP-resistance tumor growth in vivo. In conclusion, β-elemene could repress tumor growth and drug resistance via exosomal METTL3-m6A-ARF6 axis.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":"2047-2058"},"PeriodicalIF":1.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142724579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}