Acta histochemica最新文献

{"title":"Inducible gankyrin overexpression drives hepatocarcinogenesis in a liver-specific zebrafish model","authors":"Zhiyuan Gong ,&nbsp;Yuxi Sun ,&nbsp;Yueh-Min Lin ,&nbsp;Jeng-Wei Lu","doi":"10.1016/j.acthis.2025.152280","DOIUrl":"10.1016/j.acthis.2025.152280","url":null,"abstract":"<div><h3>Background</h3><div>Hepatocarcinogenesis is a complex, multistep process that begins with fatty liver, progresses to fibrosis, and ultimately leads to cancer. Numerous etiological factors contribute to this progression, highlighting the importance of developing animal models to facilitate both basic and translational research aimed at discovering new therapeutic strategies. Gankyrin is a key oncoprotein involved in the genetic regulation of liver pathology.</div></div><div><h3>Material and method</h3><div>To investigate its oncogenic role without the need for cancer cell inoculation or drug treatment, we employed a Tet-On system to drive zebrafish <em>gankyrin</em> overexpression in hepatocytes under the control of the <em>fabp10a</em> promoter. <em>Results:</em> After eight weeks of induction, <em>fabp10a:eGFP-gankyrin</em> transgenic zebrafish spontaneously developed persistent hyperplasia, bile duct hyperplasia, and hepatocellular carcinoma (HCC), demonstrating the oncogenic potential of <em>gankyrin</em> in liver tumorigenesis. In this study, we demonstrate that <em>gankyrin</em> activation drives the progressive development of HCC in zebrafish. Liver-specific overexpression of <em>gankyrin</em> in wild-type zebrafish led to hyperplasia, bile duct hyperplasia, and HCC, establishing a robust zebrafish model for studying liver cancer. Our findings highlight the utility of this model for investigating the molecular mechanisms underlying tumorigenesis.</div></div><div><h3>Conclusion</h3><div>This study establishes a robust zebrafish model in which liver-specific overexpression of <em>gankyrin</em> induces spontaneous progression from hyperplasia to hepatocellular carcinoma. The model provides a valuable platform for investigating the molecular mechanisms of hepatocarcinogenesis and exploring potential therapeutic strategies.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"127 3","pages":"Article 152280"},"PeriodicalIF":2.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144750480","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":"HSPB1 promotes gastric cancer progression by suppressing PANoptosis","authors":"Lei Yang ,&nbsp;Miaomiao Zeng ,&nbsp;Binsheng Wang ,&nbsp;Ze Yang ,&nbsp;Bo Li ,&nbsp;Xiaoliang Zhu","doi":"10.1016/j.acthis.2025.152277","DOIUrl":"10.1016/j.acthis.2025.152277","url":null,"abstract":"<div><div>Gastric cancer (GC) remains a leading cause of cancer-related mortality worldwide, driven by molecular mechanisms that promote tumor progression and therapeutic resistance. PANoptosis, an integrated programmed cell death pathway involving apoptosis, necroptosis, and pyroptosis, has emerged as a key regulator of tumorigenesis, yet its modulation in GC is poorly understood. This study aimed to investigate the role of heat shock protein beta-1 (HSPB1) in regulating PANoptosis and its impact on GC progression, hypothesizing that HSPB1 overexpression suppresses PANoptosis to enhance tumor malignancy. We employed an integrative approach combining bioinformatics analysis of GEO (GSE54129), TCGA, and GSE15460 datasets with experimental validations. HSPB1 expression was assessed in 40 paired GC and normal tissues and multiple GC cell lines (AGS, MKN-45, NCI-N87, HGC-27, SNU-1) via qPCR, Western blot, and immunohistochemistry. Functional roles were explored by overexpressing or silencing HSPB1 in NCI-N87 and AGS cells, followed by proliferation, colony formation, migration, and apoptosis assays. In vivo effects were evaluated using a nude mouse xenograft model with shHSPB1-transfected cells, analyzing tumor growth and PANoptosis markers (P-MLKL, RIPK3, Cleaved Caspase-1, NLRP3, Cleaved Caspase-3) via Western blot, IHC, and TUNEL assays. Bioinformatics revealed HSPB1 as a PANoptosis-related prognostic biomarker, with elevated expression in GC tissues correlating with poor survival. Experimental validation confirmed HSPB1 overexpression in GC tissues and cell lines. HSPB1 overexpression enhanced proliferation, invasion, and migration while suppressing apoptosis by downregulating PANoptosis markers. Conversely, HSPB1 silencing inhibited these oncogenic traits and activated PANoptosis, significantly reducing tumor growth in vivo, accompanied by upregulated PANoptosis-related proteins and increased apoptosis.HSPB1 promotes GC progression by inhibiting PANoptosis, thereby enhancing tumor survival and aggressiveness, whereas its silencing activates these cell death pathways to suppress tumorigenesis. These findings establish HSPB1 as a critical regulator of PANoptosis in GC and a potential therapeutic target, offering new avenues for overcoming resistance and improving patient outcomes.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"127 3","pages":"Article 152277"},"PeriodicalIF":2.3,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144694552","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":"Dihydroartemisinin inhibited tongue squamous cell carcinoma progression and tongue-to-lymph node metastasis through inhibiting RalB expression","authors":"Yuman Zhang ,&nbsp;Yuting Gao ,&nbsp;Yanli Gong ,&nbsp;Yanguang Yang ,&nbsp;Yi Gong ,&nbsp;Xiaoyong Song ,&nbsp;Yajun Xiong ,&nbsp;Dan Wang ,&nbsp;Zhihan Liu ,&nbsp;Xinli Shi","doi":"10.1016/j.acthis.2025.152276","DOIUrl":"10.1016/j.acthis.2025.152276","url":null,"abstract":"<div><h3>Background</h3><div>Lymph node metastasis is a key determinant of the poor survival rate in patients with tongue squamous cell carcinoma (TSCC). Therefore, inhibiting lymph node metastasis is a primary strategy for TSCC treatment. Our previous research found that dihydroartemisinin (DHA) inhibited the migration in human tongue squamous carcinoma Cal-27 cells. However, the effect and mechanism of DHA on lymph node metastasis are unknown in TSCC.</div></div><div><h3>Methods</h3><div>The expression level of Ras related GTP binding protein B (RalB) was measured in TSCC samples by immunohistochemical staining. Wound healing, invasion, and cell adhesion assays were used to investigate cell motility. Western blot was used to investigate RalB expression level. An orthotopic nude mouse model of TSCC was established to investigate the effect and mechanism of DHA on lymph node metastasis.</div></div><div><h3>Results</h3><div>First, DHA inhibited the progression of tongue tumor and tongue-to-lymph node metastasis of TSCC. Secondly, DHA inhibited RalB expression level <em>in vitro</em> and <em>in vivo</em>. Finally, DHA inhibited tongue-to-lymph node metastasis through <em>RALB</em>.</div></div><div><h3>Conclusions</h3><div>DHA inhibited tongue-to-lymph node metastasis through <em>RALB</em>, providing a novel therapeutic strategy for TSCC metastasis.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"127 3","pages":"Article 152276"},"PeriodicalIF":2.3,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144522216","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":"Corrigendum to “AARS1-mediated Osterix lactylation promotes its transcriptional activity during osteoblast differentiation” [Acta Histochem. 127 (2025) 152273]","authors":"Feige Nian ,&nbsp;Linfeng Guo ,&nbsp;Zhangli Fei ,&nbsp;Mingfeng Yang ,&nbsp;Lihong Chen ,&nbsp;Ye Zhang ,&nbsp;Zhufeng Zhang ,&nbsp;Yezhou Qian ,&nbsp;Bin Zhang","doi":"10.1016/j.acthis.2025.152275","DOIUrl":"10.1016/j.acthis.2025.152275","url":null,"abstract":"","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"127 3","pages":"Article 152275"},"PeriodicalIF":2.4,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144482827","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":"Calcipotriol inhibits the proliferation of psoriasis HaCaT cells by activating the ferroptosis pathway","authors":"Lei Yang ,&nbsp;Yue Zhang ,&nbsp;Jiansong Wu ,&nbsp;Lei Wang ,&nbsp;Shan Liu ,&nbsp;Li Zhou ,&nbsp;Jigang Zhang ,&nbsp;Chengxin Li","doi":"10.1016/j.acthis.2025.152274","DOIUrl":"10.1016/j.acthis.2025.152274","url":null,"abstract":"<div><div>Calcipotriol is a well-established treatment for psoriasis and other dermatological conditions. This study aimed to investigate whether calcipotriol exerts its therapeutic effects through ferroptosis and to elucidate its underlying molecular mechanisms using bioinformatics and cellular experiments. Differentially expressed genes (DEGs) and their functional enrichment were analyzed in psoriatic skin lesions using bioinformatics. A lipopolysaccharide (LPS)-induced HaCaT cell model was established to simulate psoriatic inflammation. The effects of calcipotriol at various concentrations and time points on HaCaT cell proliferation, apoptosis, and expression of key markers were assessed. Additionally, ferrostatin-1 (a ferroptosis inhibitor) and RSL3 (a ferroptosis inducer) were used to evaluate ferroptosis-related changes, including cell proliferation, apoptosis, reactive oxygen species (ROS) levels, glutathione (GSH) content (via ELISA), and protein expression of GPX4 and Ki-67 (via Western blot). Bioinformatics analysis revealed significant differential expression of ferroptosis-related genes, such as GPX4 and SLC7A11, in psoriatic lesions. Calcipotriol treatment inhibited HaCaT cell proliferation in a dose- and time-dependent manner, elevated ROS levels, and reduced GSH, GPX4, and Ki-67 expression. These effects were reversed by ferrostatin-1, which restored antioxidant defenses and cell viability. Conversely, RSL3 increased ROS levels and partially negated the protective effects of ferrostatin-1. These findings suggest that calcipotriol regulates ferroptosis-related gene expression and inhibits keratinocyte proliferation through induction of oxidative stress and ferroptosis, offering new insights into its mechanism of action in psoriasis treatment.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"127 3","pages":"Article 152274"},"PeriodicalIF":2.3,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144338776","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":"AARS1-mediated Osterix lactylation promotes its transcriptional activity during osteoblast differentiation","authors":"Feige Nian ,&nbsp;Linfeng Guo ,&nbsp;Zhangli Fei ,&nbsp;Mingfeng Yang ,&nbsp;Lihong Chen ,&nbsp;Ye Zhang ,&nbsp;Bin Zhang ,&nbsp;Yezhou Qian ,&nbsp;Zhufeng Zhang","doi":"10.1016/j.acthis.2025.152273","DOIUrl":"10.1016/j.acthis.2025.152273","url":null,"abstract":"<div><div>AARS1 is a newly reported lactyl-transferase that plays vital roles in tumorigenesis and innate immune response. However, the function of AARS1-mediated lactylation in osteoblast differentiation is still unclear. Here, we found that silencing of AARS1 impaired the ALP activity and formation of mineralized nodules during osteoblast differentiation. Additionally, our findings demonstrated that AARS1 catalyzed lactylation of Osterix (Osx), a crucial transcription factor involved in the differentiation process of osteoblast cells. Lactylation of Osx increased its binding to target genes and promoted the interaction between Osx and WDR5, facilitating H3K4 tri-methylation on downstream target genes. This in turn enhanced the expression of Osx target genes and osteoblast differentiation. In summary, our study revealed a novel role of AARS1-mediated Osx lactylation during osteoblast differentiation.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"127 3","pages":"Article 152273"},"PeriodicalIF":2.3,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144253587","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":"Retraction notice to “Targeting TEAD would be a potential strategy for scarless wound repair: A preliminary study\" [ Acta Histochem. 127 (2025), 152223]","authors":"Ming-Yan Yang ,&nbsp;Hong-Yuan Quan ,&nbsp;Da-Lei Li ,&nbsp;Jian Ruan ,&nbsp;Hua-Ying Fan","doi":"10.1016/j.acthis.2025.152271","DOIUrl":"10.1016/j.acthis.2025.152271","url":null,"abstract":"","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"127 3","pages":"Article 152271"},"PeriodicalIF":2.4,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144265025","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":"Characterization of immune cells in the rat intestinal mucosa and liver involved in inflammation caused by LPS and evaluation of the effects of N-acetylcysteine and disulfiram (well-known sulfur drugs) for this inflammation","authors":"Anthea Miller ,&nbsp;Giorgia Pia Lombardo ,&nbsp;Laura Spiccia ,&nbsp;Valentina Natale ,&nbsp;Alba Migliorato ,&nbsp;Marek Bednarski ,&nbsp;Małgorzata Iciek ,&nbsp;Anna Bilska-Wilkosz ,&nbsp;Mateusz Sablik ,&nbsp;Eugenia Rita Lauriano ,&nbsp;Magdalena Kotańska ,&nbsp;Simona Pergolizzi","doi":"10.1016/j.acthis.2025.152272","DOIUrl":"10.1016/j.acthis.2025.152272","url":null,"abstract":"<div><div>Lipopolysaccharide (LPS)-induced inflammation is an experimental rat model often used as a tool for testing new drugs as candidates for treating various diseases associated with inflammation. New methods now allow for precise imaging of tissues and changes induced by various factors. To increase knowledge about LPS-induced inflammation and promote strategies for investigating new therapies, this study aims to characterize immune cells involved in inflammation in the rat intestinal mucosa and liver and to evaluate the therapeutic effect of two well-known sulfur drugs N-acetylcysteine (NAC) and disulfiram (DSF) on this model LPS was administered intraperitoneally to rats once a day, for 10 days. NAC and DSF were administered 5 h after LPS. At the end of experiment, animals were euthanized, and the intestine and liver were collected. The immune cells of the intestinal mucosa and liver were characterized with the following antibodies: Toll-like receptors (TLR2 and TLR4), smooth muscle alpha-actin (α-SMA), major histocompatibility complex II (MHC-II), and serotonin (5-HT). In samples obtained from inflamed rat intestinal mucosa, it was possible to detect TLR2-positive and TLR4-positive cells, and numerous α-SMA-positive cells, indicating an inflammatory state. Furthermore, an increase in serotonin positive neuroendocrine cells compared to normal was demonstrated, which could be associated with intestinal inflammation. The number of these positive cells was much smaller in the samples derived from animals treated with NAC or DSF, suggesting anti-inflammatory action of these drugs. In the inflamed rat liver, several immune cells positive for these antibodies were observed and NAC or DSF decreased the amount of these positive cells. In conclusion, this study shows that bacterial LPS can activate various innate immune system cell populations, such as dendritic cells, neutrophils, Kupffer cells, myofibroblasts and enterocytes. Moreover, this study demonstrates the beneficial effects on NAC and DSF in alleviating inflammation and relieving tissue fibrosis in the LPS-induced inflammation in the rat intestinal mucosa and liver.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"127 3","pages":"Article 152272"},"PeriodicalIF":2.3,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144223494","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":"Exosomal delivery of AZD5582 to overcome TRAIL resistance as an optimal therapy against triple-negative breast cancer","authors":"Wanting Zhang ,&nbsp;Quanjiang Li ,&nbsp;Rui Tian ,&nbsp;Zhujie Deng ,&nbsp;Ronghui Sun ,&nbsp;Xiubin Kuang ,&nbsp;Jun Peng ,&nbsp;Bin Xie ,&nbsp;Chen Huang ,&nbsp;Zhengqiang Yuan","doi":"10.1016/j.acthis.2025.152270","DOIUrl":"10.1016/j.acthis.2025.152270","url":null,"abstract":"<div><div>Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer that lacks effective targeted therapies mainly due to drug resistance. Therefore, there is an urgent need to develop highly effective therapeutic strategies for TNBC. Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis in transformed and cancerous cells, indicating its potential for anti-cancer therapy. Unfortunately, the clinical trials of recombinant TRAIL (rTRAIL) had actually failed due to the very common TRAIL resistance in cancers. Exosomal delivery of TRAIL (EV-T) has been shown to greatly improve the cytotoxicity of TRAIL. Moreover, the TRAIL resistance was closely correlated with the upregulation of inhibitors of apoptosis proteins (IAPs) in cancer cells. As a potent antagonist of IAPs, AZD5582 (AZD) was previously shown to drastically sensitize TRAIL response. Herein, we hypothesize that AZD may be loaded into EV-T for co-delivery of AZD and TRAIL to make a synergistic combination anticancer therapy against TNBC. First, TRAIL-expressing mesenchymal stem cells (MSCs) were used to prepare EV-Ts. Then, AZD was loaded into EV-T by ultrasound to prepare the composite nanodrug AZD@EV-T. EV encapsulation significantly improved AZD stability and cellular delivery efficiency, leading to the synergistically augmented cytotoxicity and apoptosis induction in both breast and kidney cancer cell lines, whilst sparing the normal MSCs. The potential mechanisms underlying the synergism appeared to be associated with the concomitant upregulation of death receptor 5 (DR5) and expressional suppression of various anti-apoptotic factors. Importantly, the AZD@EV-T therapy triggered strikingly enhanced growth inhibition and apoptosis in the subcutaneously established BT549 xenograft tumors, consequently leading to the complete tumor regression. It also demonstrated significant potential for treating kidney cancer in A498 kidney tumor organoids. Together, AZD@EV-T effectively overcomes TRAIL resistance and may represent a highly effective and innovative anticancer therapy for both TNBC and kidney cancers.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"127 3","pages":"Article 152270"},"PeriodicalIF":2.3,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144131386","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":"Lysophosphatidic acid (LPA) receptor signaling enhances malignant potential in highly migratory lung cancer cells under hypoxic conditions","authors":"Moemi Tamura,&nbsp;Miwa Takai,&nbsp;Mao Yamamoto,&nbsp;Narumi Yashiro,&nbsp;Anri Taniguchi,&nbsp;Yuka Kusumoto,&nbsp;Shion Nagano,&nbsp;Nanami Shimomura,&nbsp;Toshifumi Tsujiuchi","doi":"10.1016/j.acthis.2025.152268","DOIUrl":"10.1016/j.acthis.2025.152268","url":null,"abstract":"<div><div>Hypoxia contributes to tumor progression, promoting cancer cell motility, invasion and metastasis. Lysophosphatidic acid (LPA) receptors are implicated in the pathogenesis of cancer. In this study, we investigated the role of LPA receptor signaling in modulating malignant behavior under hypoxic conditions (1 % O₂) in lung cancer cells. We generated highly migratory A549-R12 cells from the parental lung cancer A549 cells for this purpose. <em>LPAR1</em> and <em>LPAR2</em> expression levels were lower in both A549 and A549-R12 cells cultured at 1 % O₂ compared to those cultured at 21 % O₂, while <em>LPAR3</em> expression remained unchanged between the two cell lines. Cell motility increased in both A549 and A549-R12 cells cultured at 1 % O₂. Notably, A549-R12 cells exhibited greater motility under 1 % O₂ conditions than A549 cells. Treatment with AM966 (an LPA₁ antagonist) and (2S)-OMPT (an LPA₃ agonist) further increased the motility of A549-R12 cells, while GRI-977143 (an LPA₂ agonist) decreased their motility. Moreover, the invasion activity of A549-R12 cells was higher than that of A549 cells, with 1 % O₂ conditions significantly enhancing A549-R12 cell invasion. AM966 and (2S)-OMPT stimulated, whereas GRI-977143 inhibited, the invasion of A549-R12 cells. In the presence of LPA, cell viability to cisplatin (CDDP) was higher in A549-R12 cells cultured at both 21 % and 1 % O₂ compared to A549 cells. These results suggest that LPA receptor signaling plays a key role in regulating malignant progression in highly migratory lung cancer cells under hypoxic conditions.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"127 3","pages":"Article 152268"},"PeriodicalIF":2.3,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144123613","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}