Experimental cell research最新文献_第5页

IF 3.5 3区生物学 Q3 CELL BIOLOGY

Experimental cell research

Pub Date : 2026-01-01

引用次数: 0

IF 3.5 3区生物学 Q3 CELL BIOLOGY

Experimental cell research

Pub Date : 2026-01-01

引用次数: 0

MICA/B-driven NK cell dysfunction promotes cervical cancer via Toll signaling MICA/ b驱动的NK细胞功能障碍通过收费信号促进宫颈癌。

IF 3.5 3区生物学 Q3 CELL BIOLOGY

Experimental cell research

Pub Date : 2025-12-29 DOI: 10.1016/j.yexcr.2025.114876

Hatila Tuerxun , JinQiu Li , Qian Liu , Mikrban Tursun , Jin BaoXiao , Chengwei Wang , Ayshamgul Hasim

The immune status is of crucial importance in the development of cervical cancer (CC). MICA/B, as a major histocompatibility complex Class I associated protein, mediates anti-tumor immunity by activating NK cell receptors. However, the precise mechanisms underlying MICA/B-mediated regulation of CC progression remain poorly understood. This study combined spatial transcriptome sequencing and bioinformatics analysis and found that MICA/B was significantly highly expressed in CC tissues and cells, accompanied by more NK cell infiltration. Flow cytometry and Cell Functional assays, Knockdown of MICA/MICB weakens the activation receptor efficacy of NK cells, enhances the inhibitory signal, leads to a decrease in cytotoxicity, and simultaneously upregulates Cyclin expression in CC cells while downregulating BCL-2/BAX. Tumor xenograft models indicated that tumors with MICA knockdown exhibited a growth tendency in the presence of natural killer (NK) cells. Mechanistically, MICA/B regulates inflammatory factors such as IL-6 and CXCL10/11 through the Toll-like signaling pathway, affecting the function of NK cells. Thus, MICA/B expression on cervical cancer cells plays a pivotal role in eliciting NK cell-mediated antitumor immunity. Their downregulation attenuates NK cell function, promoting cervical cancer cell proliferation and survival via the Toll signaling pathway. These findings highlight the potential of targeting MICA/B-NK cell interactions as a therapeutic strategy for cervical cancer.

免疫状态在宫颈癌（CC）的发展中起着至关重要的作用。MICA/B是一种主要的组织相容性复合体I类相关蛋白，通过激活NK细胞受体介导抗肿瘤免疫。然而，MICA/ b介导的CC进展调控的确切机制仍然知之甚少。本研究结合空间转录组测序和生物信息学分析发现，MICA/B在CC组织和细胞中显著高表达，并伴有更多NK细胞浸润。流式细胞术和细胞功能分析显示，MICA/MICB的敲低可减弱NK细胞的激活受体作用，增强抑制信号，降低细胞毒性，同时上调CC细胞中Cyclin的表达，下调BCL-2/BAX的表达。肿瘤异种移植模型表明，MICA敲低的肿瘤在自然杀伤细胞（NK）存在下表现出生长趋势。MICA/B通过toll样信号通路调控IL-6、CXCL10/11等炎症因子，影响NK细胞功能。因此，MICA/B在宫颈癌细胞上的表达在NK细胞介导的抗肿瘤免疫中起关键作用。它们的下调会减弱NK细胞的功能，通过Toll信号通路促进宫颈癌细胞的增殖和存活。这些发现突出了靶向MICA/B-NK细胞相互作用作为宫颈癌治疗策略的潜力。

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引用次数: 0

Integrin β1 contributes to acute pancreatitis by mediating macrophage adhesion and inflammatory cascades 整合素β1通过介导巨噬细胞粘附和炎症级联反应参与急性胰腺炎。

IF 3.5 3区生物学 Q3 CELL BIOLOGY

Experimental cell research

Pub Date : 2025-12-27 DOI: 10.1016/j.yexcr.2025.114883

Yansong Xu , Yuansong Sun , Chunlin Yin , Fei Xie , He Li

Acute pancreatitis (AP) exhibits marked clinical heterogeneity. To investigate the molecular mechanisms involved in AP, we integrated bioinformatics analysis of public sequencing datasets, which identified differentially expressed genes (DEGs) significantly associated with AP. Subsequently, GO/KEGG enrichment analyses revealed robust involvement of these DEGs in cellular adhesion and MAPK signaling pathways. Protein-protein interaction (PPI) network analysis pinpointed integrin β1 (ITGB1) as the central hub gene, while single-gene gene set enrichment analysis (GSEA) across ontological databases confirmed its significant enrichment in pathways associated with adhesion and inflammation. These findings establish ITGB1 as a pivotal regulator coordinating cell adhesion and inflammatory responses in AP. In murine AP models, ITGB1 protein was significantly upregulated in the pancreas and co-localized specifically with macrophages. In vitro studies using bone marrow-derived macrophages (BMDMs) revealed that ITGB1 upregulation enhanced macrophage-endothelial adhesion and inflammatory cascades through p38 MAPK phosphorylation. Critically, clinical translation studies established the dual diagnostic value of ITGB1. The receiver operating characteristic (ROC) curve exhibited significant discriminatory power for distinguishing patients with AP from healthy controls, along with robust efficacy in stratifying disease severity. In conclusion, ITGB1 orchestrates macrophage-mediated inflammation through p38 MAPK-dependent mechanisms and can function as a biomarker for diagnosis and severity stratification in AP.

急性胰腺炎（AP）表现出明显的临床异质性。为了研究AP的分子机制，我们整合了公共测序数据集的生物信息学分析，发现了与AP显著相关的差异表达基因（deg）。随后，GO/KEGG富集分析揭示了这些deg在细胞粘附和MAPK信号通路中的强大参与。蛋白质-蛋白质相互作用（PPI）网络分析确定整合素β1 （ITGB1）为中心枢纽基因，而跨本体论数据库的单基因基因集富集分析（GSEA）证实其在与粘附和炎症相关的途径中显著富集。这些发现证实ITGB1是AP中协调细胞粘附和炎症反应的关键调节因子。在小鼠AP模型中，ITGB1蛋白在胰腺中显著上调，并特异性地与巨噬细胞共定位。利用骨髓源性巨噬细胞（bmdm）进行的体外研究显示，ITGB1上调可通过p38 MAPK磷酸化增强巨噬细胞内皮粘附和炎症级联反应。重要的是，临床翻译研究确立了ITGB1的双重诊断价值。受试者工作特征（ROC）曲线在区分AP患者和健康对照者方面显示出显著的区别力，在区分疾病严重程度方面也具有强大的功效。总之，ITGB1通过p38 mapk依赖机制协调巨噬细胞介导的炎症，可以作为AP诊断和严重程度分层的生物标志物。

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引用次数: 0

GNA15 as a potential prognostic and immunological biomarker in ccRCC based on bioinformatics analysis and experimental verification 基于生物信息学分析和实验验证的GNA15作为ccRCC潜在的预后和免疫学生物标志物。

IF 3.5 3区生物学 Q3 CELL BIOLOGY

Experimental cell research

Pub Date : 2025-12-25 DOI: 10.1016/j.yexcr.2025.114874

Xiumin Xu , Zeping Zuo , Jinhai Zhu , Jun Wu , Tao Zhang

As the most common and aggressive subtype of renal cancer, clear cell renal cell carcinoma (ccRCC) often shows poor responsiveness to current therapeutic strategies. Although GNA15, a G protein alpha subunit, has been associated with the progression of multiple tumor types, its functional significance in ccRCC remains largely undefined. Public datasets were used to profile GNA15 expression across cancers, and its links to prognosis, genomic diversity, stemness, and immune infiltration were analyzed with multiple computational tools. In ccRCC, transcriptomic and protein expression levels were validated using immunofluorescence and western blotting. Functional assays, including colony formation, transwell migration, tumor spheroid formation, and GSEA, were used to investigate the biological role of GNA15. The effects of GNA15 knockdown were assessed in renal cancer cell lines. GNA15 was aberrantly upregulated in multiple cancers and significantly elevated in ccRCC tissues and cell lines. High GNA15 expression correlated with poor overall survival and advanced clinical stage. It was also positively associated with tumor heterogeneity, stemness, and immunosuppressive microenvironment characteristics, particularly M2 macrophage and neutrophil infiltration. GSEA identified enrichment in oncogenic pathways, including JAK-STAT, Wnt, and Notch signaling. In vitro knockdown of GNA15 reduced tumor cell proliferation, migration, spheroid formation, and expression of stemness markers and PD-L1. Our results highlight GNA15 as a novel oncogenic and immune-related contributor to ccRCC progression, supporting its potential as a prognostic biomarker and therapeutic target.

作为肾癌中最常见和最具侵袭性的亚型，透明细胞肾细胞癌（ccRCC）通常对当前的治疗策略反应较差。尽管GNA15（一种G蛋白α亚基）与多种肿瘤类型的进展有关，但其在ccRCC中的功能意义仍未明确。使用公共数据集分析GNA15在癌症中的表达，并使用多种计算工具分析其与预后、基因组多样性、干性和免疫浸润的联系。在ccRCC中，使用免疫荧光和western blotting验证转录组学和蛋白质表达水平。功能分析，包括集落形成、跨井迁移、肿瘤球体形成和GSEA，用于研究GNA15的生物学作用。研究了GNA15基因敲低对肾癌细胞系的影响。GNA15在多种癌症中异常上调，在ccRCC组织和细胞系中显著升高。GNA15高表达与总生存期差、临床分期晚期相关。它还与肿瘤异质性、干性和免疫抑制微环境特征呈正相关，特别是M2巨噬细胞和中性粒细胞浸润。GSEA发现在致癌途径中富集，包括JAK-STAT、Wnt和Notch信号。体外敲除GNA15可降低肿瘤细胞的增殖、迁移、球状体的形成以及干细胞标志物和PD-L1的表达。我们的研究结果强调了GNA15作为ccRCC进展的一种新的致癌和免疫相关因子，支持其作为预后生物标志物和治疗靶点的潜力。

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引用次数: 0

Corrigendum to “m6A-mediated upregulation of miRNA-193a aggravates cardiomyocyte apoptosis and inflammatory response in sepsis-induced cardiomyopathy via the METTL3/ miRNA-193a/BCL2L2 pathway” [Exp Cell Res. 2023 Sep 1; 430(1): 113712] “m6a介导的miRNA-193a上调通过METTL3/ miRNA-193a/BCL2L2途径加重败血症诱导的心肌病心肌细胞凋亡和炎症反应”的更正[Exp Cell Res. 2023 Sep 1；430(1): 113712。

IF 3.5 3区生物学 Q3 CELL BIOLOGY

Experimental cell research

Pub Date : 2025-12-24 DOI: 10.1016/j.yexcr.2025.114856

Lian Liang , Siqi Liu , Qingyu Wu , Ran Chen , Shanping Jiang , Zhengfei Yang

引用次数: 0

Neutrophil extracellular traps promote epithelial-mesenchymal transition in COPD via the RAGE/PI3K/AKT pathway 中性粒细胞胞外陷阱通过RAGE/PI3K/AKT通路促进COPD的上皮-间质转化。

IF 3.5 3区生物学 Q3 CELL BIOLOGY

Experimental cell research

Pub Date : 2025-12-24 DOI: 10.1016/j.yexcr.2025.114869

Jiawei Zou , Lin Chen , Yang Yang , Zengyu Huo , Yuhong Liu , Zhijuan Luo , Siyi Ou , Cunlai Xu , Jing Bai

Neutrophil extracellular traps (NETs) play a critical role in smoking-related chronic airway inflammation. However, it remains unknown whether NETs promote COPD progression by affecting epithelial-mesenchymal transition (EMT). This study aimed to investigate the correlation between serum biomarker profiles and pulmonary function in COPD patients, elucidate the relationship between NETs formation and EMT in COPD lung tissue, and explore the effect of cigarette smoke extract (CSE)-induced NETs on EMT in bronchial epithelial cells and its molecular mechanisms. We found that COPD patients showed decreased serum DNase-I and elevated IL-6, TNF-α, dsDNA, and MPO-DNA levels. COPD lung tissues exhibited increased NETs accumulation and altered EMT-related protein expression. In vitro, CSE-NETs treatment altered the gene expression profile of BEAS-2B cells, activating the RAGE/PI3K/AKT signaling pathway and promoting EMT. Inhibition of RAGE or PI3K attenuated CSE-NETs-induced EMT. In vivo, DNase-I and CI-amidine Attenuate Emphysema and EMT in Cigarette Smoke–Induced COPD Mice by Reducing NETs. This study reveals the critical role of CSE-induced-NETs in the pathogenesis of COPD and identifies the RAGE/PI3K/AKT signaling pathway as a potential therapeutic target, providing new insights for COPD treatment.

中性粒细胞胞外陷阱（NETs）在吸烟相关的慢性气道炎症中起关键作用。然而，尚不清楚NETs是否通过影响上皮-间质转化（EMT）促进COPD进展。本研究旨在探讨COPD患者血清生物标志物谱与肺功能的相关性，阐明COPD肺组织NETs形成与EMT的关系，探讨香烟烟雾提取物（CSE）诱导的NETs对支气管上皮细胞EMT的影响及其分子机制。我们发现COPD患者血清dna - i降低，IL-6、TNF-α、dsDNA和MPO-DNA水平升高。COPD肺组织表现出NETs积累增加和emt相关蛋白表达改变。在体外，CSE-NETs处理改变了BEAS-2B细胞的基因表达谱，激活了RAGE/PI3K/AKT信号通路，促进了EMT。抑制RAGE或PI3K可减弱cse - nets诱导的EMT。在体内，dna - i和ci -脒通过减少NETs减轻香烟烟雾诱导的COPD小鼠的肺气肿和EMT。本研究揭示了cse诱导的nets在COPD发病机制中的关键作用，并确定了RAGE/PI3K/AKT信号通路作为潜在的治疗靶点，为COPD的治疗提供了新的见解。

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引用次数: 0

Targeting the Gas6-TAM-SOCS1/3 axis: CP-25 attenuates macrophage dysfunction in primary Sjögren's syndrome 靶向Gas6-TAM-SOCS1/3轴：CP-25减轻原发性Sjögren综合征中的巨噬细胞功能障碍

IF 3.5 3区生物学 Q3 CELL BIOLOGY

Experimental cell research

Pub Date : 2025-12-23 DOI: 10.1016/j.yexcr.2025.114871

Yun Chen , Qianwen Tian , Meng Yang , Yunxin Zhang , Fuxue Kuang , Lejie Sun , Qi Xi , Wendong Xu , Hongfei Cai , Yukang Mao , Tao Wang , Wei Wei , Huaxun Wu

The etiology of primary Sjögren's syndrome (pSS) remains largely unexplained to date, and there is a relative lack of effective clinical treatment options.This study aimed to explore the potential therapeutic mechanism of paeoniflorin-6′-O-benzenesulfonate (CP-25) for pSS, especially regarding whether it exerts its effect by regulating the Gas6/TAM signaling axis. The study assessed the expression of the Gas6/TAM axis and its association with macrophage polarization using labial gland tissues, peripheral blood samples from patients with primary Sjögren's syndrome (pSS), and an experimental Sjögren's syndrome mouse model. In vitro, RAW264.7 cells and submandibular gland epithelial cells were employed to analyze changes in the TAM-SOCS1/3 axis, JAK1-STAT1 pathway, and polarization markers (iNOS, Arg1). ELISA was used to detect Gas6 secretion by SGECs, while flow cytometry and confocal microscopy evaluated macrophage function.Both primary Sjögren's syndrome patients and experimental Sjögren's syndrome mice showed dysregulation of the Gas6/TAM signaling pathway, which was closely linked to macrophage polarization imbalance.CP-25 alleviated ESS mouse symptoms by activating the TAM-SOCS1/3 axis, inhibiting the JAK1-STAT1 pathway, and promoting M2 macrophage polarization. In vitro experiments confirmed that CP-25 stimulated salivary gland epithelial cells (SGECs) to secrete Gas6 and reduced matrix metalloproteinase-9 (MMP-9) expression. Moreover, exogenous Gas6 promoted M2 polarization via TAM receptor activation; knockdown of the Mer receptor impaired macrophage phagocytic function. The study also indicated that MMP-9 may be involved in regulating TAM receptors on macrophages.In conclusion, CP-25 treats pSS by regulating SGEC Gas6/MMP-9 secretion, targeting macrophage TAM-SOCS1/3, modulating JAK1-STAT1, and restoring macrophage function.

迄今为止，原发性Sjögren综合征（pSS）的病因在很大程度上仍未得到解释，并且相对缺乏有效的临床治疗方案。本研究旨在探讨芍药苷-6′-邻苯磺酸盐（CP-25）对pSS的潜在治疗机制，特别是其是否通过调节Gas6/TAM信号轴发挥作用。该研究通过唇腺组织、原发性Sjögren综合征（pSS）患者外周血样本和实验性Sjögren综合征小鼠模型，评估了Gas6/TAM轴的表达及其与巨噬细胞极化的关系。在体外，采用RAW264.7细胞和颌下腺上皮细胞分析TAM-SOCS1/3轴、JAK1-STAT1通路和极化标记物（iNOS, Arg1）的变化。ELISA检测sges分泌Gas6，流式细胞术和共聚焦显微镜检测巨噬细胞功能。原发性Sjögren综合征患者和实验性Sjögren综合征小鼠均出现Gas6/TAM信号通路失调，这与巨噬细胞极化失衡密切相关。CP-25通过激活TAM-SOCS1/3轴，抑制JAK1-STAT1通路，促进M2巨噬细胞极化，缓解ESS小鼠症状。体外实验证实，CP-25刺激唾液腺上皮细胞（SGECs）分泌Gas6，降低基质金属蛋白酶-9 （MMP-9）表达。此外，外源Gas6通过激活TAM受体促进M2极化；敲低Mer受体会损害巨噬细胞的吞噬功能。本研究还提示MMP-9可能参与巨噬细胞上TAM受体的调节。综上所述，CP-25通过调节SGEC Gas6/MMP-9分泌，靶向巨噬细胞TAM-SOCS1/3，调节JAK1-STAT1，恢复巨噬细胞功能来治疗pSS。

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引用次数: 0

FBXL6 drives tumorigenesis in lung adenocarcinoma through ubiquitination and proteasomal degradation of CDKN1C FBXL6通过泛素化和蛋白酶体降解CDKN1C驱动肺腺癌的肿瘤发生。

IF 3.5 3区生物学 Q3 CELL BIOLOGY

Experimental cell research

Pub Date : 2025-12-22 DOI: 10.1016/j.yexcr.2025.114872

Guanzhong Dong, Ning Zhang, Dong Yang, Zibo Zhu, Yi He

Lung adenocarcinoma (LUAD) is a highly prevalent and lethal malignancy. Although F-box and leucine-rich repeat protein 6 (FBXL6), an E3 ubiquitin ligase, has been implicated in tumor progression across certain cancers, its functional role in LUAD remains unclear. In this study, we investigated the oncogenic potential of FBXL6 in LUAD pathogenesis. Bioinformatics analysis of GEO, TCGA, and TNM datasets revealed significant upregulation of FBXL6 in LUAD tissues. Functional studies using FBXL6-knockdown (via shRNA in PC-9 cells) and FBXL6-overexpressing (via plasmid transfection in A549 cells) demonstrated that FBXL6 depletion suppressed cell proliferation, migration, and invasion, whereas its overexpression reversed these effects. In vivo experiments further confirmed that FBXL6 knockdown in PC-9 cells inhibited tumor growth and liver metastasis in BALB/c nude mice following subcutaneous or tail vein injection. Mechanistically, FBXL6 was found to physically interact with cyclin-dependent kinase inhibitor 1C (CDKN1C/p57Kip2) and promote its polyubiquitination and proteasomal degradation, thereby destabilizing this tumor suppressor. Rescue assays validated that CDKN1C mediates the pro-tumorigenic effects of FBXL6 on LUAD cell proliferation and metastasis. Collectively, our findings reveal that FBXL6 drives LUAD progression by ubiquitinating and degrading CDKN1C, highlighting its potential as a therapeutic target for LUAD.

肺腺癌（LUAD）是一种非常普遍和致命的恶性肿瘤。虽然F-box和富亮氨酸重复蛋白6 (FBXL6)，一种E3泛素连接酶，与某些癌症的肿瘤进展有关，但其在LUAD中的功能作用尚不清楚。在本研究中，我们研究了FBXL6在LUAD发病机制中的致癌潜力。GEO、TCGA和TNM数据集的生物信息学分析显示，FBXL6在LUAD组织中显著上调。FBXL6敲低（在PC-9细胞中通过shRNA）和FBXL6过表达（在A549细胞中通过质粒转染）的功能研究表明，FBXL6缺失抑制细胞增殖、迁移和侵袭，而其过表达逆转了这些作用。体内实验进一步证实，PC-9细胞中FBXL6敲低可抑制BALB/c裸鼠皮下或尾静脉注射后的肿瘤生长和肝脏转移。在机制上，FBXL6被发现与细胞周期蛋白依赖性激酶抑制剂1C （CDKN1C/p57Kip2）物理相互作用，促进其多泛素化和蛋白酶体降解，从而破坏这种肿瘤抑制因子的稳定。救援实验证实CDKN1C介导FBXL6对LUAD细胞增殖和转移的促瘤作用。总的来说，我们的研究结果表明FBXL6通过泛素化和降解CDKN1C来驱动LUAD的进展，突出了其作为LUAD治疗靶点的潜力。

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引用次数: 0

p38 MAPK-mediated suppression of Nrf2-MPC2 axis drives metabolic reprogramming which confers imatinib resistance in blast crisis phase of chronic myeloid leukemia p38 mapk介导的Nrf2-MPC2轴抑制驱动代谢重编程，在慢性髓性白血病细胞危象期赋予伊马替尼耐药。

IF 3.5 3区生物学 Q3 CELL BIOLOGY

Experimental cell research

Pub Date : 2025-12-19 DOI: 10.1016/j.yexcr.2025.114870

Manish Bhat , Mythreyi Narasimhan , Ashutosh Shelar , Raghavendra Patwardhan , Santosh Kumar Sandur , Rukmini Govekar

Background

Metabolic reprogramming is a hallmark of cancer and its role in tumour drug resistance is emerging. This study explored its role in resistance to tyrosine kinase inhibitors (TKIs) in the blast crisis (BC) phase of chronic myeloid leukemia (CML), which occurs despite inactivation of the oncogenic Bcr-Abl by TKIs. We previously reported that this Bcr-Abl-independent resistance is mimicked in TKI-resistant CML-BC cell line and is causally associated with p38MAPK, a known modulator of metabolism. Thus, we investigated whether p38MAPK-mediated metabolic rewiring caused resistance in CML-BC.

Methods

Imatinib sensitive and resistant CML-BC cell lines K562 and KU812 were analysed for metabolic proteins by Western blotting, metabolome by mass spectrometry, and apoptosis, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) by flow cytometry. Sequence of alterations was established by inhibition and knockdown studies.

Results

TKI-resistant cells exhibited enhanced glucose uptake, increased levels of GLUT1, glycolytic enzymes, and those of pyruvate and ATP which reduced upon inhibition of GLUT1, indicative of enhanced glycolysis as contributor of energy. In contrast, the cells displayed reduced NADH/NAD ratio, MMP, mitochondrial ROS which resulted in reduction in apoptotic population. Inhibition studies revealed that suppression of hyperphosphorylated p38MAPK-mediated activation of Nrf2, caused reduced mitochondrial pyruvate carrier (MPC2) expression. MPC2 inhibition in sensitive cells recapitulated the resistant phenotype with reduced MMP and ROS levels.

Conclusion

p38MAPK-mediated suppression of Nrf2/MPC2 axis abrogates mitochondrial function and ROS-mediated cell death while enhanced glycolysis generates ATP to sustain growth. The resultant pro-survival conditions allow leukemic cell survival under drug pressure causing resistance.

背景：代谢重编程是癌症的一个标志，它在肿瘤耐药中的作用正在逐渐显现。本研究探讨了其在慢性髓性白血病（CML）细胞危化期（BC）中对酪氨酸激酶抑制剂（TKIs）耐药的作用，尽管TKIs使致癌的Bcr-Abl失活。我们之前报道过，这种bcr - abl无关的耐药在tki耐药CML-BC细胞系中被模拟，并且与p38MAPK（一种已知的代谢调节剂）有因果关系。因此，我们研究了p38mapk介导的代谢重布线是否引起CML-BC的耐药性。方法：对CML-BC细胞株K562和KU812进行伊马替尼敏感和耐药细胞株的代谢蛋白和代谢组学检测，流式细胞术检测细胞凋亡、线粒体膜电位（MMP）和活性氧（ROS）。通过抑制和敲低研究确定了改变序列。结果：tki耐药细胞表现出葡萄糖摄取增强，GLUT1、糖酵解酶水平升高，丙酮酸和ATP水平在GLUT1抑制后降低，表明糖酵解作为能量来源增强。相反，细胞表现出NADH/NAD比率、MMP、线粒体ROS降低，导致凋亡群体减少。抑制研究表明，抑制高磷酸化p38mapk介导的Nrf2激活导致线粒体丙酮酸载体（MPC2）表达降低。敏感细胞的MPC2抑制再现了耐药表型，降低了MMP和ROS水平。结论：p38mapk介导的Nrf2/MPC2轴抑制消除线粒体功能和ros介导的细胞死亡，而糖酵解增强产生ATP维持生长。由此产生的促生存条件允许白血病细胞在药物压力下存活，从而产生耐药性。

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引用次数: 0