[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-332682-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-332682-en":130},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":74,"head_meta":76,"extra_data":78,"updated_unix":80},105,"en","inhibition-of-p2rx7-contributes-to-cytotoxicity-by-suppression-of-glycolysis-and-akt-activation-in-human-hepatocellular-carcinoma","Inhibition of P2RX7 contributes to cytotoxicity by suppression of glycolysis and AKT activation in human hepatocellular carcinoma","","This study investigates how blocking the purinergic receptor P2RX7 affects human hepatocellular carcinoma cell survival and metabolism. P2RX7 gene and protein levels are elevated in HCC tumor cells. Pharmacological inhibition with the selective antagonist A-804598 and genetic knockdown of P2RX7 suppress glycolysis by reducing hexokinase 2 (HK2) and induce cytotoxicity through inhibited AKT activation. Increased caspase-3 activation supports apoptosis-related cell death.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/research-report/","Research & Report",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/inhibition-of-p2rx7-contributes-to-cytotoxicity-by-suppression-of-glycolysis-and-akt-activation-in-human-hepatocellular-carcinoma/332682/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/inhibition-of-p2rx7-contributes-to-cytotoxicity-by-suppression-of-glycolysis-and-akt-activation-in-human-hepatocellular-carcinoma/332682.png","ImageObject",300,407,{"name":42,"@type":43},"Sage","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-29","2026-09-21",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",6,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"How is P2RX7 involved in hepatocellular carcinoma?","Question",{"text":63,"@type":64},"P2RX7 is linked to tumor proliferation, invasion, metastatic dissemination, and clinical outcomes. Its role in glucose metabolism and HCC survival has been unclear prior to this study.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"What happens to glycolysis when P2RX7 is inhibited?",{"text":68,"@type":64},"Inhibition of P2RX7 using A-804598 or P2RX7 knockdown suppresses glycolytic activity by reducing hexokinase 2 (HK2) levels.",{"name":70,"@type":61,"acceptedAnswer":71},"How does P2RX7 inhibition lead to cytotoxicity in HCC cells?",{"text":72,"@type":64},"A-804598 treatment and P2RX7 knockdown induce cytotoxicity by inhibiting AKT activation and increasing caspase-3 activation in human HCC cells.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},332682,1790013012,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,105,110,114,119,122,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":55,"doc_module":4,"doc_module_name":25,"category_name":102,"show_sort_weight":103,"slug":104},"Technology",50,"technology",{"id":106,"doc_module":4,"doc_module_name":25,"category_name":107,"show_sort_weight":108,"slug":109},7,"Healthcare",40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":112,"slug":113},8,30,"research-report",{"id":115,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},9,"Religion & Spirituality",20,"religion-spirituality",{"id":117,"doc_module":4,"doc_module_name":25,"category_name":120,"show_sort_weight":117,"slug":121},"World Cup","world-cup",{"id":123,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":123,"slug":125},10,"Lifestyle","lifestyle",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":97,"slug":129},19,"General","general",{"code":4,"msg":82,"data":131},{"doc_id":79,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":111,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":55,"language":139,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":12,"update_tm":143,"read_time":144,"preview_page_count":4},687197207057,"https://ap-avatar.wpscdn.com/davatar_29158cc5080c5b710cf443261637dec0","BMB Reports  \nBMB Rep. 2024; 57(10): 459-464  \n[www.bmbreports.org](www.bmbreports.org)  \nInhibition of P2RX7 contributes to cytotoxicity by suppression of glycolysis and AKT activation in human hepatocellular carcinoma  \nJae Kook Yang1,\\#, Junhyung Kim2,\\#, Young Hyeon Ahn1, Sang Ho Bae3, Moo-Jun Baek3, Sae Hwan Lee1, * & Jong-Seok Moon2,4, *  \n1Department of Internal Medicine, Soonchunhyang University College of Medicine Cheonan Hospital, Cheonan 31151, 2Department of Integrated Biomedical Science, Soonchunhyang Institute of Medi-Bio Science (SIMS), Soonchunhyang University, Cheonan 31151, 3Department of Surgery, Soonchunhyang University College of Medicine Cheonan Hospital, Cheonan 31151, 4Department of Pathology, College of Medicine, Soonchunhyang University, Cheonan 31151, Korea  \nHepatocellular carcinoma (HCC) is the most common form of primary liver cancer. HCC occurs people with chronic liver diseases. The purinergic receptor P2X 7 (P2RX7) is involved in tumor proliferation and growth. Also, P2RX7 is associated with tumor invasion and metastatic dissemination. High glucose utilization is important for the survival of various types of tumors. However, the role of P2RX7 in glucose metabolism and cellular survival of HCC remains unclear. Here, our results show that the gene and protein levels of P2RX7 were elevated in tumor cells of patients with HCC. The pharmacological inhibition of P2RX7 by A-804598, a selective P2RX7 antagonist, and genetic inhibition by P2RX7 knockdown suppressed the glycolytic activity by reduction of hexokinase 2 (HK2), a key enzyme of the glycolysis pathway, in human HCC cells. Also, both A-804598 treatment and P2RX7 knockdown induced cytotoxicity via inhibition of AKT activation which is critical for tumor cell survival in human HCC cells. Moreover, A-804598 treatment and P2RX7 knockdown increased cytotoxicity and caspase-3 activation in human HCC cells. These results suggest that inhibition of P2RX7 contributes to cytotoxicity by suppression of glycolysis and AKT activation in human HCC.[BMB Reports 2024; 57(10): 459-464]  \nINTRODUCTION  \nHepatocellular carcinoma (HCC) is the sixth most diagnosed  \n*Corresponding authors. Jong-Seok Moon, Tel: +82-41-413-5022; Fax: +82-41-413-5006; [E-mail: jongseok81@sch.ac.kr](E-mail: jongseok81@sch.ac.kr); Sae Hwan Lee, Tel: +82-41-570-3677; Fax: +82-41-470-3728; E-mail: [stevesh@sch.ac.kr](stevesh@sch.ac.kr)  \n\\#These authors contributed equally to this work. [https://doi.org/10.5483/BMBRep.2024-0070](https://doi.org/10.5483/BMBRep.2024-0070)  \nReceived 10 May 2024, Revised 7 July 2024,  \nAccepted 1 September 2024, Published online 4 October 2024 Keywords: AKT, Caspase-3, Glycolysis, HCC, P2RX7  \ncancer (1), and a leading cause of death via cancer (1, 2) . The main risk factor of HCC is chronic liver diseases, including hepatitis viral infection, nonalcoholic fatty liver disease (NAFLD), chronic alcohol consumption, and all causes of cirrhosisinducing conditions (3, 4) .  \nHigh glucose utilization is critical for cellular proliferation, growth, and homeostasis in various types of tumors (5, 6) . High glucose consumption is associated with tumorigenicity, tumor aggressiveness, and tumor growth, and is linked to multiple branched pathways through the glycolytic pathway for the synthesis of biomacromolecules in HCC cells (7, 8) . Hexokinase 2 (HK2) is the major isoform of hexokinase in cancers (9) . HK2 promotes the cellular uptake and utilization of glucose and is expressed in various cancer cells (10) . During glucose utilization, HK2 is activated during hepatocarcinogenesis, and it correlates with poor overall survival in HCC (7, 8, 11, 12) .  \nThe purinergic receptor P2X 7 (P2RX7) is a ligand-gated cation channel and is stimulated in response to extracellular adenosine 5'–triphosphate (ATP) binding (13) . P2RX7 regulates various downstream events in a cell-dependent manner, such as inflammatory response, cell proliferation, cell death, cellular metabolism, a","cbCaictQVRi5D2Yk","https://ap.wps.com/l/cbCaictQVRi5D2Yk","pdf",8473198,"English","# INTRODUCTION\n## Background on HCC and glucose metabolism\n## P2RX7 function and relevance to HCC\n## Study rationale and main findings","[{\"question\":\"How is P2RX7 involved in hepatocellular carcinoma?\",\"answer\":\"P2RX7 is linked to tumor proliferation, invasion, metastatic dissemination, and clinical outcomes. Its role in glucose metabolism and HCC survival has been unclear prior to this study.\"},{\"question\":\"What happens to glycolysis when P2RX7 is inhibited?\",\"answer\":\"Inhibition of P2RX7 using A-804598 or P2RX7 knockdown suppresses glycolytic activity by reducing hexokinase 2 (HK2) levels.\"},{\"question\":\"How does P2RX7 inhibition lead to cytotoxicity in HCC cells?\",\"answer\":\"A-804598 treatment and P2RX7 knockdown induce cytotoxicity by inhibiting AKT activation and increasing caspase-3 activation in human HCC cells.\"}]","Inhibition of P2RX7 contributes to cytotoxicity by suppression of glycolysis and AKT activation in human hepatocellular carcinoma | PDF",1789999062,15]