Clinical and Experimental Pharmacology and Physiology最新文献_第5页

In vitro effects and mathematical modelling of CTCE-9908 (a chemokine receptor 4 antagonist) on melanoma cell survival CTCE-9908（一种趋化因子受体 4 拮抗剂）对黑色素瘤细胞存活的体外效应和数学建模

IF 2.9 4区医学

Clinical and Experimental Pharmacology and Physiology Pub Date : 2024-05-01 DOI: 10.1111/1440-1681.13865

Charlise Basson, Avulundiah Edwin Phiri, Manjunath Gandhi, Roumen Anguelov, June Cheptoo Serem, Priyesh Bipath, Yvette Nkondo Hlophe

{"title":"In vitro effects and mathematical modelling of CTCE-9908 (a chemokine receptor 4 antagonist) on melanoma cell survival","authors":"Charlise Basson, Avulundiah Edwin Phiri, Manjunath Gandhi, Roumen Anguelov, June Cheptoo Serem, Priyesh Bipath, Yvette Nkondo Hlophe","doi":"10.1111/1440-1681.13865","DOIUrl":"https://doi.org/10.1111/1440-1681.13865","url":null,"abstract":"CTCE-9908, a CXC chemokine receptor 4 (CXCR4) antagonist, prevents CXCR4 phosphorylation and inhibits the interaction with chemokine ligand 12 (CXCL12) and downstream signalling pathways associated with metastasis. This study evaluated the in vitro effects of CTCE-9908 on B16 F10 melanoma cells with the use of mathematical modelling. Crystal violet staining was used to construct a mathematical model of CTCE-9908 B16 F10 (melanoma) and RAW 264.7 (non-cancerous macrophage) cell lines on cell viability to predict the half-maximal inhibitory concentration (IC50). Morphological changes were assessed using transmission electron microscopy. Flow cytometry was used to assess changes in cell cycle distribution, apoptosis via caspase-3, cell survival via extracellular signal-regulated kinase1/2 activation, CXCR4 activation and CXCL12 expression. Mathematical modelling predicted IC50 values from 0 to 100 h. At IC50, similar cytotoxicity between the two cell lines and ultrastructural morphological changes indicative of cell death were observed. At a concentration 10 times lower than IC50, CTCE-9908 induced inhibition of cell survival (p = 0.0133) in B16 F10 cells but did not affect caspase-3 or cell cycle distribution in either cell line. This study predicts CTCE-9908 IC50 values at various time points using mathematical modelling, revealing cytotoxicity in melanoma and non-cancerous cells. CTCE-9908 significantly inhibited melanoma cell survival at a concentration 10 times lower than the IC50 in B16 F10 cells but not RAW 264.7 cells. However, CTCE-9908 did not affect CXCR4 phosphorylation, apoptosis, or cell cycle distribution in either cell line.","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1440-1681.13865","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140818851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Curcumol reduces lower limb arteriosclerosis in rats by inhibiting human arterial smooth muscle cell activity 姜黄醇通过抑制人体动脉平滑肌细胞活性减轻大鼠下肢动脉硬化症

IF 2.9 4区医学

Clinical and Experimental Pharmacology and Physiology Pub Date : 2024-04-29 DOI: 10.1111/1440-1681.13867

Shengzhuang Yang, Gaosheng Huang, Xiangsen Liang, Yu Sun, Lei Xian

{"title":"Curcumol reduces lower limb arteriosclerosis in rats by inhibiting human arterial smooth muscle cell activity","authors":"Shengzhuang Yang, Gaosheng Huang, Xiangsen Liang, Yu Sun, Lei Xian","doi":"10.1111/1440-1681.13867","DOIUrl":"https://doi.org/10.1111/1440-1681.13867","url":null,"abstract":"Cardiovascular diseases, particularly those involving arterial stenosis and smooth muscle cell proliferation, pose significant health risks. This study aimed to investigate the therapeutic potential of curcumol in inhibiting platelet-derived growth factor-BB (PDGF-BB)-induced human aortic smooth muscle cell (HASMC) proliferation, migration and autophagy. Using cell viability assays, 5-ethynyl-2′-deoxyuridine (EdU) incorporation assays and Western Blot analyses, we observed that curcumol effectively attenuated PDGF-BB-induced HASMC proliferation and migration in a concentration-dependent manner. Furthermore, curcumol mitigated PDGF-BB-induced autophagy, as evidenced by the downregulation of LC3-II/LC3-I ratio and upregulation of P62. In vivo experiments using an arteriosclerosis obliterans model demonstrated that curcumol treatment significantly ameliorated arterial morphology and reduced stenosis. Additionally, curcumol inhibited the activity of the KLF5/COX2 axis, a key pathway in vascular diseases. These findings suggest that curcumol has the potential to serve as a multi-target therapeutic agent for vascular diseases.","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140814298","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}

引用次数: 0

N6-methyladenosine methylation on FSCN1 mediated by METTL14/IGF2BP3 contributes to human papillomavirus type 16-infected cervical squamous cell carcinoma 由 METTL14/IGF2BP3 介导的 FSCN1 上的 N6-甲基腺苷甲基化是人类乳头瘤病毒 16 型感染宫颈鳞状细胞癌的诱因之一

IF 2.9 4区医学

Clinical and Experimental Pharmacology and Physiology Pub Date : 2024-04-28 DOI: 10.1111/1440-1681.13864

Qingqing Tian, Juqing Huang, Qin Zhang, Jufen Zhao

{"title":"N6-methyladenosine methylation on FSCN1 mediated by METTL14/IGF2BP3 contributes to human papillomavirus type 16-infected cervical squamous cell carcinoma","authors":"Qingqing Tian, Juqing Huang, Qin Zhang, Jufen Zhao","doi":"10.1111/1440-1681.13864","DOIUrl":"https://doi.org/10.1111/1440-1681.13864","url":null,"abstract":"Human papillomavirus (HPV) infection has been reported to be associated with N6-methyladenosine (m6A) modification in cancers. However, the underlying mechanism by which m6A methylation participates in HPV-related cervical squamous cell carcinoma (CSCC) remains largely unclear. In this study, we observed that m6A regulators methyltransferase like protein (METTL14) and insulin like growth factor 2 mRNA binding protein 3 (IGF2BP3) were upregulated in HPV-positive CSCC tissues and cell lines, and their high expression predicted poor prognosis for HPV-infected CSCC patients. Cellular functional experiments verified that HPV16 oncogenes E6/E7 upregulated the expression of METTL14 and IGF2BP3 to promote cell proliferation and epithelial mesenchymal transition of CSCC cells. Next, we found that E6/E7 stabilized fascin actin-bundling protein 1 (FSCN1) mRNA and elevated FSCN1 expression in CSCC cells through upregulating METTL14/IGF2BP3-mediated m6A modification, and FSCN1 expression was also validated to be positively associated with worse outcomes of HPV-positive CSCC patients. Finally, HPV16-positive CSCC cell lines SiHa and CaSki were transfected with knockdown vector for E6/E7 or METTL14/IGF2BP3 and overexpressing vector for FSCN1, and functional verification experiments were performed through using MTT assay, flow cytometry, wound healing assay and tumour formation assay. Results indicated that knockdown of E6/E7 or METTL14/IGF2BP3 suppressed cell proliferation, migration and tumorigenesis, and accelerated cell apoptosis of HPV-positive CSCC cells. Their tumour-suppressive effects were abolished through overexpressing FSCN1. Overall, HPV E6/E7 advanced CSCC development through upregulating METTL14/IGF2BP3-mediated FSCN1 m6A modification.","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140808155","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}

引用次数: 0

A spontaneous hyperglycaemic cynomolgus monkey presents cognitive deficits, neurological dysfunction and cataract 一只自发性高血糖猴出现认知障碍、神经功能紊乱和白内障

IF 2.9 4区医学

Clinical and Experimental Pharmacology and Physiology Pub Date : 2024-04-22 DOI: 10.1111/1440-1681.13863

Hongdi Huang, Jianglin Pu, Yufang Zhou, Yang Fan, Yali Zhang, Yanling Li, Yangzhuo Chen, Yun Wang, Xiaomei Yu, Bulgin Dmitry, Zhu Zhou, Jianhong Wang

{"title":"A spontaneous hyperglycaemic cynomolgus monkey presents cognitive deficits, neurological dysfunction and cataract","authors":"Hongdi Huang, Jianglin Pu, Yufang Zhou, Yang Fan, Yali Zhang, Yanling Li, Yangzhuo Chen, Yun Wang, Xiaomei Yu, Bulgin Dmitry, Zhu Zhou, Jianhong Wang","doi":"10.1111/1440-1681.13863","DOIUrl":"https://doi.org/10.1111/1440-1681.13863","url":null,"abstract":"Chronic hyperglycaemia is a chief feature of diabetes mellitus and complicates with many systematic anomalies. Non-human primates (NHPs) are excellent for studying hyperglycaemia or diabetes and associated comorbidities, but lack behavioural observation. In the study, behavioural, brain imaging and histological analysis were performed in a case of spontaneously hyperglycaemic (HGM) Macaca fascicularis. The results were shown that the HGM monkey had persistent body weight loss, long-term hyperglycaemia, insulin resistance, dyslipidemia, but normal concentrations of insulin, C-peptide, insulin autoantibody, islet cell antibody and glutamic acid decarboxylase antibody. Importantly, an impaired working memory in a delayed response task and neurological dysfunctions were found in the HGM monkey. The tendency for atrophy in hippocampus was observed by magnetic resonance imaging. Lenticular opacification, lens fibres disruptions and vacuole formation also occurred to the HGM monkey. The data suggested that the spontaneous HGM monkey might present diabetes-like characteristics and associated neurobehavioral anomalies in this case. This study first reported cognitive deficits in a spontaneous hyperglycaemia NHPs, which might provide evidence to use macaque as a promising model for translational research in diabetes and neurological complications.","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140633850","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}

引用次数: 0

Association between dietary inflammation index and inflammatory bowel disease in adults: Results from National Health and Nutrition Examination Survey 2009–2010 成人膳食炎症指数与炎症性肠病之间的关系：2009-2010 年全国健康与营养调查的结果

IF 2.9 4区医学

Clinical and Experimental Pharmacology and Physiology Pub Date : 2024-04-21 DOI: 10.1111/1440-1681.13859

Jing-yi Zhu, Xiao-ru Sun, Mu-yun Liu, Chang Sun

{"title":"Association between dietary inflammation index and inflammatory bowel disease in adults: Results from National Health and Nutrition Examination Survey 2009–2010","authors":"Jing-yi Zhu, Xiao-ru Sun, Mu-yun Liu, Chang Sun","doi":"10.1111/1440-1681.13859","DOIUrl":"https://doi.org/10.1111/1440-1681.13859","url":null,"abstract":"Previous study has demonstrated that the Dietary Inflammation Index (DII) played a role in the risk of inflammatory bowel disease (IBD), however, the prevalence and risk factors for IBD are distinct across locations and groups, and therefore, the findings are debatable and warrant further investigation. A total of 4363 participants were calculated in the National Health and Nutrition Examination Survey (NHANES) 2009 to 2010, of whom 1.21% self-reported a history of IBD. DII values were performed as a good predictor of dietary inflammation based on data from two 24-h dietary reviews in the NHANES database. Comparing the multifarious effects along with variations of the whole population by grouping populations according to DII quartiles, dietary inflammation levels increased progressively from DII quartile 1(Q1) to quartile 4(Q4). The association between DII and IBD was tested with multi-variable logistic regression models, subgroup analyses and weighted generalized additive models. Participants in the Q4 group showed the highest levels of C-reactive protein and reduced haemoglobin and albumin levels. Logistic regression confirmed the odds ratios (95% confidence intervals) of IBD for DII were 0.99 (0.86, 1.15), 0.97 (0.84, 1.13) and 0.80 (0.66, 0.98) in models 1, 2 and 3, respectively. The negative correlation between DII and IBD among United States adults from the NHANES database became increasingly apparent as covariates were adjusted. Subgroup analyses and smoothed curve fitting confirmed the inverse results. The study revealed that DII was correlated with the overall physical well-being of participants. However, there was no significant association between DII and IBD.","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140631991","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}

引用次数: 0

Correction to “GSK3β inhibitor TDZD8 ameliorates brain damage through both ROS scavenging and inhibition of apoptosis in hyperglycemic subarachnoid haemorrhage rats” 对 "GSK3β抑制剂TDZD8通过清除高血糖蛛网膜下腔出血大鼠体内的ROS和抑制细胞凋亡改善脑损伤 "的更正

IF 2.9 4区医学

Clinical and Experimental Pharmacology and Physiology Pub Date : 2024-04-18 DOI: 10.1111/1440-1681.13853

引用次数: 0

Loganin exerts neuroprotective effect by inhibiting neuronal pyroptosis in rat with cerebral haemorrhage 罗加宁通过抑制脑出血大鼠神经元的脓毒症发挥神经保护作用

IF 2.9 4区医学

Clinical and Experimental Pharmacology and Physiology Pub Date : 2024-04-18 DOI: 10.1111/1440-1681.13858

Yu Wang, Min Zhao, Jing Li, Yue Liu

{"title":"Loganin exerts neuroprotective effect by inhibiting neuronal pyroptosis in rat with cerebral haemorrhage","authors":"Yu Wang, Min Zhao, Jing Li, Yue Liu","doi":"10.1111/1440-1681.13858","DOIUrl":"https://doi.org/10.1111/1440-1681.13858","url":null,"abstract":"Intracerebral haemorrhage (ICH) presents significant challenges in clinical management because of the high morbidity and mortality, necessitating novel therapeutic approaches. This study aimed to assess the neuroprotective effects of loganin in a rat ICH model. Sprague–Dawley rats were used, subjected to a collagenase-induced ICH model, followed by loganin treatment at doses of 2.5, 5 and 10 mg/kg. Neurological functions were evaluated using the modified neurological severity score (mNSS) and a rotarod test. Results indicated a significant improvement in neurological functions in loganin-treated groups, evident from the mNSS and rotarod tests, suggesting dose-dependent neuroprotection. Loganin also effectively reduced the blood–brain barrier (BBB) permeability and cerebral oedema. Additionally, it mitigated cellular pyroptosis, as shown by terminal deoxynucleotidyl transferase dUTP nick-end labelling staining and western blot analysis, which indicated reduced levels of pyroptosis markers in treated rats. Furthermore, loganin's regulatory effects on the adenosine A2A receptor and myosin light chain kinase pathways were observed, potentially underpinning its protective mechanism against ICH. The study concludes that loganin exhibits significant neuroprotective properties in a rat ICH model, highlighting its potential as a novel therapeutic strategy. Despite promising results, the study needs further research to determine loganin's therapeutic potential in human ICH patients. This research paves the way for further exploration into loganin's clinical applications, potentially revolutionizing treatment strategies for patients suffering from intracerebral haemorrhage.","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140619746","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}

引用次数: 0

Salvianic acid A sodium facilitates cardiac microvascular endothelial cell proliferation by enhancing the hypoxia-inducible factor-1 alpha/vascular endothelial growth factor signalling pathway post-myocardial infarction 丹酚酸 A 钠通过增强心肌梗死后缺氧诱导因子-1 α/血管内皮生长因子信号通路，促进心脏微血管内皮细胞增殖

IF 2.9 4区医学

Clinical and Experimental Pharmacology and Physiology Pub Date : 2024-04-18 DOI: 10.1111/1440-1681.13855

Jichun Liu, Fei Wu, Zhenhan Li, Shengwei Zheng, Yanqiang Huang, Hao Chen

{"title":"Salvianic acid A sodium facilitates cardiac microvascular endothelial cell proliferation by enhancing the hypoxia-inducible factor-1 alpha/vascular endothelial growth factor signalling pathway post-myocardial infarction","authors":"Jichun Liu, Fei Wu, Zhenhan Li, Shengwei Zheng, Yanqiang Huang, Hao Chen","doi":"10.1111/1440-1681.13855","DOIUrl":"https://doi.org/10.1111/1440-1681.13855","url":null,"abstract":"Cardiac microvascular endothelial cells (CMECs) are important cells surrounding the cardiomyocytes in the heart that maintain microenvironment homeostasis. Salvianic acid A sodium (SAAS) has been reported to prevent myocardial infarction (MI) injury. However, the role of SAAS on CMEC proliferation remains unclear. CEMCs exposed to oxygen glucose deprivation (OGD) were used to explore the angiogenic abilities of SAAS. In vivo, C57BL/6 mice were divided into three groups: sham, MI and SAAS + MI groups. Compared to OGD group, SAAS led to a reduction in the apoptotic rate and an increase of the proliferation in vitro. Additionally, SAAS increased the protein levels of Bcl2, HIF-1α and vascular endothelial growth factor (VEGF) with the reduction of Bax. In terms of the specific mechanisms, SAAS might inhibit HIF-1α ubiquitination and enhance the HIF-1α/VEGF signalling pathway to increase CMEC proliferation. Furthermore, SAAS increased the density of vessels, inhibited myocardial fibrosis and improved cardiac dysfunction in vivo. The present study has revealed that SAAS could potentially be used as an active substance to facilitate CMEC proliferation post-MI.","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140619748","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}

引用次数: 0

Metformin ameliorates endometrial thickness in a rat model of thin endometrium 二甲双胍可改善大鼠薄子宫内膜模型中的子宫内膜厚度

IF 2.9 4区医学

Clinical and Experimental Pharmacology and Physiology Pub Date : 2024-04-15 DOI: 10.1111/1440-1681.13862

M. Imran, Aditya Khandvilkar, Siddhanath Metkari, Geetanjali Sachdeva, Uddhav Chaudhari

{"title":"Metformin ameliorates endometrial thickness in a rat model of thin endometrium","authors":"M. Imran, Aditya Khandvilkar, Siddhanath Metkari, Geetanjali Sachdeva, Uddhav Chaudhari","doi":"10.1111/1440-1681.13862","DOIUrl":"https://doi.org/10.1111/1440-1681.13862","url":null,"abstract":"Metformin, a well-established anti-diabetic drug, is also used in managing various other metabolic disorders including polycystic ovarian syndrome (PCOS). There are evidences to show that metformin improves endometrial functions in PCOS women. However, fewer studies have explored the direct effects of metformin on endometrium. Previous in vitro studies have shown that therapeutic serum concentrations of metformin enhance endometrial epithelial cell proliferation. The present study was undertaken to investigate in vivo effects of metformin on endometrial proliferation in a rat model of thin endometrium. Toward this, a rat model of thin endometrium was developed. Metformin (0.1% or 1% w/v) was administrated orally for 15 days in rats with thin endometrium. Oral metformin administration for three consecutive estrous cycles (15 days) in the thin endometrium rat model led to an increase in endometrial thickness compared to sham endometrium. Histological analysis showed a significant increase in the number of endometrial glands (P < 0.05), stromal cells (P < 0.01) and blood vessels (P < 0.01) in metformin-treated (n = 10 in each group) uterine horns compared to sham (saline-treated) uterine horns in rats. The expression of proliferating cell nuclear antigen and vascular epithelial growth factor was found to be upregulated on treatment with 1% metformin-treated group (n = 7). However, pregnancy outcomes in the rats treated with metformin remained unaltered despite the restoration of endometrial thickness. In conclusion, the study demonstrated that metformin ameliorates endometrial thickness in a rat model of thin endometrium by increasing endometrial proliferation and angiogenesis, without restoration of embryo implantation.","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140556154","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}

引用次数: 0

Colorectal cancer cells with stably expressed SIRT3 demonstrate proliferating retardation by Wnt/β-catenin cascade inactivation 稳定表达 SIRT3 的结直肠癌细胞因 Wnt/β-catenin 级联失活而增殖迟缓

IF 2.9 4区医学

Clinical and Experimental Pharmacology and Physiology Pub Date : 2024-04-15 DOI: 10.1111/1440-1681.13856

Tianyu Li, Leqi Fan, Yijiang Jia, Chen Xu, Wei Guo, Yuji Wang, Ye Li

{"title":"Colorectal cancer cells with stably expressed SIRT3 demonstrate proliferating retardation by Wnt/β-catenin cascade inactivation","authors":"Tianyu Li, Leqi Fan, Yijiang Jia, Chen Xu, Wei Guo, Yuji Wang, Ye Li","doi":"10.1111/1440-1681.13856","DOIUrl":"https://doi.org/10.1111/1440-1681.13856","url":null,"abstract":"Colorectal cancer (CRC) is a typical and lethal digestive system malignancy. In this study, we investigated the effect of sirtuin 3 (SIRT3) expression, a fidelity mitochondrial protein, on the proliferation of CRC cells and the mechanisms involved. Using the University of Alabama at Birmingham Cancer Data Analysis Portal database and the Clinical Proteomic Tumour Analysis Consortium database, we discovered that low expression of SIRT3 in CRC was a negative factor for survival prognosis (P < .05). Meanwhile, SIRT3 expression was correlated with distant metastasis and tumour, node, metastasis stage of CRC patients (P < .05). Subsequently, we observed that CRC cells with stable SIRT3 expression exhibited a significant decrease in proliferative capacities both in vitro and in vivo, compared to their counterparts (P < .05). Further investigation using western blot, immunoprecipitation and TOPflash/FOPflash assay showed the mechanism of growth retardation of these cells was highly associated with the degradation of β-catenin in cytosol, and the localization of β-catenin/α-catenin complex in the nucleus. In conclusion, our findings suggest that the inhibition of CRC cell proliferation by SIRT3 is closely associated with the inactivation of the Wnt/β-catenin signalling pathway.","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140556306","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}

引用次数: 0