Zafer Yildirim, Eda Doğan, Hale Güler Kara, Buket Kosova, Vildan Bozok
{"title":"STING 激活可提高替莫唑胺在携带 PTEN 的胶质母细胞瘤细胞中的效率。","authors":"Zafer Yildirim, Eda Doğan, Hale Güler Kara, Buket Kosova, Vildan Bozok","doi":"10.55730/1300-0144.5828","DOIUrl":null,"url":null,"abstract":"<p><strong>Background/aim: </strong>Glioblastoma is one of the most aggressive tumours, resistant to all applied therapy regiments and prone to relapse. Median survival rates are therefore only expressed as months. STING agonists are immunomodulatory molecules that activate type I interferon expression, making them potentially useful in regulating the tumour microenvironment. Since PTEN serves as a critical phosphatase in activating interferon-regulating transcription factors and is frequently mutated in glioblastoma cells, this study aimed to investigate STING activation in glioblastoma cell lines, examining whether they harbour the PTEN protein or not.°.</p><p><strong>Materials and methods: </strong>T98G and U118MG glioblastoma cell lines were treated with the 2'3'-c-di-AM(PS)2(Rp,Rp) STING agonist together with or without the chemotherapeutic agent temozolomide. cGAS/STING pathway components were subsequently analysed using qRT-PCR, western blot, and ELISA methods.</p><p><strong>Results: </strong>Our results showed that PTEN-harbouring T98G cells responded well to STING activation, leading to increased temozolomide efficacy. In contrast, STING activation in U118MG cells did not affect the response to temozolomide. mRNA expression levels of <i>STING</i>, <i>IRF3</i>, <i>NF-KB</i>, and <i>RELA</i> genes were significantly increased at the combined treatment groups in T98G cell line. Conversely, combined treatment with STING agonist and temozolomide did not affect mRNA expression levels of cGAS/STING pathway genes in U118MG cells.</p><p><strong>Conclusion: </strong>Our data offers new evidence suggesting that STING agonists can effectively be used to increase temozolomide response in the presence of PTEN protein. Therefore, increased GBM therapy success rates can be achieved by employing the PTEN expression status as a predictive biomarker before treating patients with a chemotherapeutic agent in combination with STING agonist.</p>","PeriodicalId":23361,"journal":{"name":"Turkish Journal of Medical Sciences","volume":null,"pages":null},"PeriodicalIF":1.2000,"publicationDate":"2024-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11265881/pdf/","citationCount":"0","resultStr":"{\"title\":\"STING activation increases the efficiency of temozolomide in PTEN harbouring glioblastoma cells.\",\"authors\":\"Zafer Yildirim, Eda Doğan, Hale Güler Kara, Buket Kosova, Vildan Bozok\",\"doi\":\"10.55730/1300-0144.5828\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background/aim: </strong>Glioblastoma is one of the most aggressive tumours, resistant to all applied therapy regiments and prone to relapse. Median survival rates are therefore only expressed as months. STING agonists are immunomodulatory molecules that activate type I interferon expression, making them potentially useful in regulating the tumour microenvironment. Since PTEN serves as a critical phosphatase in activating interferon-regulating transcription factors and is frequently mutated in glioblastoma cells, this study aimed to investigate STING activation in glioblastoma cell lines, examining whether they harbour the PTEN protein or not.°.</p><p><strong>Materials and methods: </strong>T98G and U118MG glioblastoma cell lines were treated with the 2'3'-c-di-AM(PS)2(Rp,Rp) STING agonist together with or without the chemotherapeutic agent temozolomide. cGAS/STING pathway components were subsequently analysed using qRT-PCR, western blot, and ELISA methods.</p><p><strong>Results: </strong>Our results showed that PTEN-harbouring T98G cells responded well to STING activation, leading to increased temozolomide efficacy. In contrast, STING activation in U118MG cells did not affect the response to temozolomide. mRNA expression levels of <i>STING</i>, <i>IRF3</i>, <i>NF-KB</i>, and <i>RELA</i> genes were significantly increased at the combined treatment groups in T98G cell line. Conversely, combined treatment with STING agonist and temozolomide did not affect mRNA expression levels of cGAS/STING pathway genes in U118MG cells.</p><p><strong>Conclusion: </strong>Our data offers new evidence suggesting that STING agonists can effectively be used to increase temozolomide response in the presence of PTEN protein. Therefore, increased GBM therapy success rates can be achieved by employing the PTEN expression status as a predictive biomarker before treating patients with a chemotherapeutic agent in combination with STING agonist.</p>\",\"PeriodicalId\":23361,\"journal\":{\"name\":\"Turkish Journal of Medical Sciences\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.2000,\"publicationDate\":\"2024-01-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11265881/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Turkish Journal of Medical Sciences\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.55730/1300-0144.5828\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"MEDICINE, GENERAL & INTERNAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Turkish Journal of Medical Sciences","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.55730/1300-0144.5828","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"MEDICINE, GENERAL & INTERNAL","Score":null,"Total":0}
STING activation increases the efficiency of temozolomide in PTEN harbouring glioblastoma cells.
Background/aim: Glioblastoma is one of the most aggressive tumours, resistant to all applied therapy regiments and prone to relapse. Median survival rates are therefore only expressed as months. STING agonists are immunomodulatory molecules that activate type I interferon expression, making them potentially useful in regulating the tumour microenvironment. Since PTEN serves as a critical phosphatase in activating interferon-regulating transcription factors and is frequently mutated in glioblastoma cells, this study aimed to investigate STING activation in glioblastoma cell lines, examining whether they harbour the PTEN protein or not.°.
Materials and methods: T98G and U118MG glioblastoma cell lines were treated with the 2'3'-c-di-AM(PS)2(Rp,Rp) STING agonist together with or without the chemotherapeutic agent temozolomide. cGAS/STING pathway components were subsequently analysed using qRT-PCR, western blot, and ELISA methods.
Results: Our results showed that PTEN-harbouring T98G cells responded well to STING activation, leading to increased temozolomide efficacy. In contrast, STING activation in U118MG cells did not affect the response to temozolomide. mRNA expression levels of STING, IRF3, NF-KB, and RELA genes were significantly increased at the combined treatment groups in T98G cell line. Conversely, combined treatment with STING agonist and temozolomide did not affect mRNA expression levels of cGAS/STING pathway genes in U118MG cells.
Conclusion: Our data offers new evidence suggesting that STING agonists can effectively be used to increase temozolomide response in the presence of PTEN protein. Therefore, increased GBM therapy success rates can be achieved by employing the PTEN expression status as a predictive biomarker before treating patients with a chemotherapeutic agent in combination with STING agonist.
期刊介绍:
Turkish Journal of Medical sciences is a peer-reviewed comprehensive resource that provides critical up-to-date information on the broad spectrum of general medical sciences. The Journal intended to publish original medical scientific papers regarding the priority based on the prominence, significance, and timeliness of the findings. However since the audience of the Journal is not limited to any subspeciality in a wide variety of medical disciplines, the papers focusing on the technical details of a given medical subspeciality may not be evaluated for publication.