{"title":"通过同时剥夺葡萄糖和谷氨酰胺,双星诱导胰腺癌原位治疗中的嗜热症","authors":"Xinlong Wang, Binbin Ding, Wei Liu, Lishuang Qi, Jiating Li, Xin Zheng, Yiqin Song, Qiyuan Li, Jiawen Wu, Meng Zhang, Hua Chen, Yongwei Wang, Yilong Li*, Bei Sun* and Ping’an Ma*, ","doi":"10.1021/jacs.4c03478","DOIUrl":null,"url":null,"abstract":"<p >Pancreatic cancer is a highly fatal disease, and existing treatment methods are ineffective, so it is urgent to develop new effective treatment strategies. The high dependence of pancreatic cancer cells on glucose and glutamine suggests that disrupting this dependency could serve as an alternative strategy for pancreatic cancer therapy. We identified the vital genes glucose transporter 1 (GLUT1) and alanine-serine-cysteine transporter 2 (ASCT2) through bioinformatics analysis, which regulate glucose and glutamine metabolism in pancreatic cancer, respectively. Human serum albumin nanoparticles (HSA NPs) for delivery of GLUT1 and ASCT2 inhibitors, BAY-876/V-9302@HSA NPs, were prepared by a self-assembly process. This nanodrug inhibits glucose and glutamine uptake of pancreatic cancer cells through the released BAY-876 and V-9302, leading to nutrition deprivation and oxidative stress. The inhibition of glutamine leads to the inhibition of the synthesis of the glutathione, which further aggravates oxidative stress. Both of them lead to a significant increase in reactive oxygen species, activating caspase 1 and GSDMD and finally inducing pyroptosis. This study provides a new effective strategy for orthotopic pancreatic cancer treatment by dual starvation-induced pyroptosis. The study for screening metabolic targets using bioinformatics analysis followed by constructing nanodrugs loaded with inhibitors will inspire future targeted metabolic therapy for pancreatic cancer.</p>","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":null,"pages":null},"PeriodicalIF":14.4000,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Dual Starvations Induce Pyroptosis for Orthotopic Pancreatic Cancer Therapy through Simultaneous Deprivation of Glucose and Glutamine\",\"authors\":\"Xinlong Wang, Binbin Ding, Wei Liu, Lishuang Qi, Jiating Li, Xin Zheng, Yiqin Song, Qiyuan Li, Jiawen Wu, Meng Zhang, Hua Chen, Yongwei Wang, Yilong Li*, Bei Sun* and Ping’an Ma*, \",\"doi\":\"10.1021/jacs.4c03478\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p >Pancreatic cancer is a highly fatal disease, and existing treatment methods are ineffective, so it is urgent to develop new effective treatment strategies. The high dependence of pancreatic cancer cells on glucose and glutamine suggests that disrupting this dependency could serve as an alternative strategy for pancreatic cancer therapy. We identified the vital genes glucose transporter 1 (GLUT1) and alanine-serine-cysteine transporter 2 (ASCT2) through bioinformatics analysis, which regulate glucose and glutamine metabolism in pancreatic cancer, respectively. Human serum albumin nanoparticles (HSA NPs) for delivery of GLUT1 and ASCT2 inhibitors, BAY-876/V-9302@HSA NPs, were prepared by a self-assembly process. This nanodrug inhibits glucose and glutamine uptake of pancreatic cancer cells through the released BAY-876 and V-9302, leading to nutrition deprivation and oxidative stress. The inhibition of glutamine leads to the inhibition of the synthesis of the glutathione, which further aggravates oxidative stress. Both of them lead to a significant increase in reactive oxygen species, activating caspase 1 and GSDMD and finally inducing pyroptosis. This study provides a new effective strategy for orthotopic pancreatic cancer treatment by dual starvation-induced pyroptosis. The study for screening metabolic targets using bioinformatics analysis followed by constructing nanodrugs loaded with inhibitors will inspire future targeted metabolic therapy for pancreatic cancer.</p>\",\"PeriodicalId\":49,\"journal\":{\"name\":\"Journal of the American Chemical Society\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":14.4000,\"publicationDate\":\"2024-05-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of the American Chemical Society\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://pubs.acs.org/doi/10.1021/jacs.4c03478\",\"RegionNum\":1,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of the American Chemical Society","FirstCategoryId":"92","ListUrlMain":"https://pubs.acs.org/doi/10.1021/jacs.4c03478","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
Dual Starvations Induce Pyroptosis for Orthotopic Pancreatic Cancer Therapy through Simultaneous Deprivation of Glucose and Glutamine
Pancreatic cancer is a highly fatal disease, and existing treatment methods are ineffective, so it is urgent to develop new effective treatment strategies. The high dependence of pancreatic cancer cells on glucose and glutamine suggests that disrupting this dependency could serve as an alternative strategy for pancreatic cancer therapy. We identified the vital genes glucose transporter 1 (GLUT1) and alanine-serine-cysteine transporter 2 (ASCT2) through bioinformatics analysis, which regulate glucose and glutamine metabolism in pancreatic cancer, respectively. Human serum albumin nanoparticles (HSA NPs) for delivery of GLUT1 and ASCT2 inhibitors, BAY-876/V-9302@HSA NPs, were prepared by a self-assembly process. This nanodrug inhibits glucose and glutamine uptake of pancreatic cancer cells through the released BAY-876 and V-9302, leading to nutrition deprivation and oxidative stress. The inhibition of glutamine leads to the inhibition of the synthesis of the glutathione, which further aggravates oxidative stress. Both of them lead to a significant increase in reactive oxygen species, activating caspase 1 and GSDMD and finally inducing pyroptosis. This study provides a new effective strategy for orthotopic pancreatic cancer treatment by dual starvation-induced pyroptosis. The study for screening metabolic targets using bioinformatics analysis followed by constructing nanodrugs loaded with inhibitors will inspire future targeted metabolic therapy for pancreatic cancer.
期刊介绍:
The flagship journal of the American Chemical Society, known as the Journal of the American Chemical Society (JACS), has been a prestigious publication since its establishment in 1879. It holds a preeminent position in the field of chemistry and related interdisciplinary sciences. JACS is committed to disseminating cutting-edge research papers, covering a wide range of topics, and encompasses approximately 19,000 pages of Articles, Communications, and Perspectives annually. With a weekly publication frequency, JACS plays a vital role in advancing the field of chemistry by providing essential research.