Yusuke Aoki, Qinghong Han, Yutaro Kubota, Noriyuki Masaki, Yasunori Tome, Michael Bouvet, Kotaro Nishida, Robert M Hoffman
{"title":"超级甲氨蝶呤耐药骨肉瘤细胞保留对重组蛋氨酸酶的敏感性：靶向蛋氨酸成瘾以克服极端癌症化疗耐药。","authors":"Yusuke Aoki, Qinghong Han, Yutaro Kubota, Noriyuki Masaki, Yasunori Tome, Michael Bouvet, Kotaro Nishida, Robert M Hoffman","doi":"10.21873/anticanres.17480","DOIUrl":null,"url":null,"abstract":"<p><strong>Background/aim: </strong>Drug-resistance in osteosarcoma results in a very poor clinical prognosis and has been a recalcitrant problem over many decades. We have previously reported the development of super methotrexate (MTX)-resistant osteosarcoma cells (143B-MTX<sup>SR</sup>), selected from parental 143B osteosarcoma cells (143B-P) 143B-MTX<sup>SR</sup> cells were previously selected by culturing the cells with increasing concentrations of MTX, resulting in osteosarcoma cells which are 5,500 times more MTX-resistant than the parental cells, due to extreme over-expression of dihydrofolate reductase (DHFR). In the present study, the potential therapeutic efficacy of methionine restriction, using recombinant methioninase (rMETase), was explored to overcome super MTX-resistant osteosarcoma cells.</p><p><strong>Materials and methods: </strong>Previously-selected 143B-MTX<sup>SR</sup> cells were used for the present study. Sensitivity to methionine restriction by rMETase was determined using the WST-8 assay and compared between 143B-MTX<sup>SR</sup> and parental 143B-P cells.</p><p><strong>Results: </strong>143B-MTX<sup>SR</sup> cells (rMETase IC<sub>50</sub>: 0.38 U/ml) were very sensitive to methionine restriction by rMETase, very similar to 143B-P (rMETase IC<sub>50</sub>: 0.36 U/ml).</p><p><strong>Conclusion: </strong>rMETase overcame a 5,500-fold MTX-resistance of osteosarcoma cells. The present results suggest methionine restriction by rMETase can be a potential clinical strategy to overcome recalcitrant drug-resistance in osteosarcoma.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 3","pages":"929-934"},"PeriodicalIF":1.6000,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Super Methotrexate-resistant Osteosarcoma Cells Retain Their Sensitivity to Recombinant Methioninase: Targeting Methionine Addiction to Overcome Extreme Cancer-Chemotherapy Resistance.\",\"authors\":\"Yusuke Aoki, Qinghong Han, Yutaro Kubota, Noriyuki Masaki, Yasunori Tome, Michael Bouvet, Kotaro Nishida, Robert M Hoffman\",\"doi\":\"10.21873/anticanres.17480\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background/aim: </strong>Drug-resistance in osteosarcoma results in a very poor clinical prognosis and has been a recalcitrant problem over many decades. We have previously reported the development of super methotrexate (MTX)-resistant osteosarcoma cells (143B-MTX<sup>SR</sup>), selected from parental 143B osteosarcoma cells (143B-P) 143B-MTX<sup>SR</sup> cells were previously selected by culturing the cells with increasing concentrations of MTX, resulting in osteosarcoma cells which are 5,500 times more MTX-resistant than the parental cells, due to extreme over-expression of dihydrofolate reductase (DHFR). In the present study, the potential therapeutic efficacy of methionine restriction, using recombinant methioninase (rMETase), was explored to overcome super MTX-resistant osteosarcoma cells.</p><p><strong>Materials and methods: </strong>Previously-selected 143B-MTX<sup>SR</sup> cells were used for the present study. Sensitivity to methionine restriction by rMETase was determined using the WST-8 assay and compared between 143B-MTX<sup>SR</sup> and parental 143B-P cells.</p><p><strong>Results: </strong>143B-MTX<sup>SR</sup> cells (rMETase IC<sub>50</sub>: 0.38 U/ml) were very sensitive to methionine restriction by rMETase, very similar to 143B-P (rMETase IC<sub>50</sub>: 0.36 U/ml).</p><p><strong>Conclusion: </strong>rMETase overcame a 5,500-fold MTX-resistance of osteosarcoma cells. The present results suggest methionine restriction by rMETase can be a potential clinical strategy to overcome recalcitrant drug-resistance in osteosarcoma.</p>\",\"PeriodicalId\":8072,\"journal\":{\"name\":\"Anticancer research\",\"volume\":\"45 3\",\"pages\":\"929-934\"},\"PeriodicalIF\":1.6000,\"publicationDate\":\"2025-03-01\",\"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.17480\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Anticancer research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.21873/anticanres.17480","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"ONCOLOGY","Score":null,"Total":0}
Super Methotrexate-resistant Osteosarcoma Cells Retain Their Sensitivity to Recombinant Methioninase: Targeting Methionine Addiction to Overcome Extreme Cancer-Chemotherapy Resistance.
Background/aim: Drug-resistance in osteosarcoma results in a very poor clinical prognosis and has been a recalcitrant problem over many decades. We have previously reported the development of super methotrexate (MTX)-resistant osteosarcoma cells (143B-MTXSR), selected from parental 143B osteosarcoma cells (143B-P) 143B-MTXSR cells were previously selected by culturing the cells with increasing concentrations of MTX, resulting in osteosarcoma cells which are 5,500 times more MTX-resistant than the parental cells, due to extreme over-expression of dihydrofolate reductase (DHFR). In the present study, the potential therapeutic efficacy of methionine restriction, using recombinant methioninase (rMETase), was explored to overcome super MTX-resistant osteosarcoma cells.
Materials and methods: Previously-selected 143B-MTXSR cells were used for the present study. Sensitivity to methionine restriction by rMETase was determined using the WST-8 assay and compared between 143B-MTXSR and parental 143B-P cells.
Results: 143B-MTXSR cells (rMETase IC50: 0.38 U/ml) were very sensitive to methionine restriction by rMETase, very similar to 143B-P (rMETase IC50: 0.36 U/ml).
Conclusion: rMETase overcame a 5,500-fold MTX-resistance of osteosarcoma cells. The present results suggest methionine restriction by rMETase can be a potential clinical strategy to overcome recalcitrant drug-resistance in osteosarcoma.
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.
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