Yehyeong Lee, Yonghyo Kim, Hyeran Shin, Yeong Chan Ryu, Dong-Woo Kang, Tae Il Kim, Yong-Hee Cho
{"title":"Anti-tumor Effects of Idarubicin Hydrochloride in Desmoid Tumors.","authors":"Yehyeong Lee, Yonghyo Kim, Hyeran Shin, Yeong Chan Ryu, Dong-Woo Kang, Tae Il Kim, Yong-Hee Cho","doi":"10.21873/anticanres.17359","DOIUrl":null,"url":null,"abstract":"<p><strong>Background/aim: </strong>Desmoid tumors (DTs), also referred to as aggressive fibromatosis, originate from connective tissues and typically manifest with a propensity for local invasion. Despite extensive research efforts aimed at exploring novel anti-tumor agents for DTs, the development of effective clinical management strategies remains an ongoing challenge due to the limited success of current treatments, which frequently lead to inconsistent outcomes and a high recurrence rate of DTs. To overcome these limitations, we focused our research aim on a drug repositioning approach to identify existing medications that could be effective against DTs.</p><p><strong>Materials and methods: </strong>Mouse models with Apc mutations, specifically Apc<sup>1638N/+</sup> and Apc<sup>1638N/+</sup>/Trp53<sup>-/-</sup>, were generated to study DTs. Primary desmoid cells were isolated from these models for experimental analysis. Idarubicin hydrochloride (IDH), a topoisomerase II (TOPO II) inhibitor, was tested on these primary cells, colorectal cancer (CRC) cell lines, and tumor organoids derived from Apc<sup>1638N/+</sup> mice. Cell viability was determined with the WST reagent and colony formation assay was evaluated. The anti-tumor efficacy of IDH was tested in an in vivo CRC xenograft model using HCT-116 cells.</p><p><strong>Results: </strong>The TOPO II inhibitor IDH showed significant growth inhibition effects on Apc<sup>1638N/+</sup> and Apc<sup>1638N/+</sup>/Trp53<sup>-/-</sup> cells. IDH also showed remarkable anti-tumor effects on CRC cell lines and tumor organoids derived from intestinal tumor cells of the Apc<sup>1638N/+</sup> mouse model. Furthermore, IDH exerted dramatic anti-tumor effects on an HCT-116 cell line xenograft mouse model.</p><p><strong>Conclusion: </strong>IDH could be a promising therapeutic agent for inhibiting DTs and CRC by targeting TOPO II.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"44 12","pages":"5313-5322"},"PeriodicalIF":1.6000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Anticancer research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.21873/anticanres.17359","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background/aim: Desmoid tumors (DTs), also referred to as aggressive fibromatosis, originate from connective tissues and typically manifest with a propensity for local invasion. Despite extensive research efforts aimed at exploring novel anti-tumor agents for DTs, the development of effective clinical management strategies remains an ongoing challenge due to the limited success of current treatments, which frequently lead to inconsistent outcomes and a high recurrence rate of DTs. To overcome these limitations, we focused our research aim on a drug repositioning approach to identify existing medications that could be effective against DTs.
Materials and methods: Mouse models with Apc mutations, specifically Apc1638N/+ and Apc1638N/+/Trp53-/-, were generated to study DTs. Primary desmoid cells were isolated from these models for experimental analysis. Idarubicin hydrochloride (IDH), a topoisomerase II (TOPO II) inhibitor, was tested on these primary cells, colorectal cancer (CRC) cell lines, and tumor organoids derived from Apc1638N/+ mice. Cell viability was determined with the WST reagent and colony formation assay was evaluated. The anti-tumor efficacy of IDH was tested in an in vivo CRC xenograft model using HCT-116 cells.
Results: The TOPO II inhibitor IDH showed significant growth inhibition effects on Apc1638N/+ and Apc1638N/+/Trp53-/- cells. IDH also showed remarkable anti-tumor effects on CRC cell lines and tumor organoids derived from intestinal tumor cells of the Apc1638N/+ mouse model. Furthermore, IDH exerted dramatic anti-tumor effects on an HCT-116 cell line xenograft mouse model.
Conclusion: IDH could be a promising therapeutic agent for inhibiting DTs and CRC by targeting TOPO II.
期刊介绍:
ANTICANCER RESEARCH is an independent international peer-reviewed journal devoted to the rapid publication of high quality original articles and reviews on all aspects of experimental and clinical oncology. Prompt evaluation of all submitted articles in confidence and rapid publication within 1-2 months of acceptance are guaranteed.
ANTICANCER RESEARCH was established in 1981 and is published monthly (bimonthly until the end of 2008). Each annual volume contains twelve issues and index. Each issue may be divided into three parts (A: Reviews, B: Experimental studies, and C: Clinical and Epidemiological studies).
Special issues, presenting the proceedings of meetings or groups of papers on topics of significant progress, will also be included in each volume. There is no limitation to the number of pages per issue.