Sei Morinaga, Qinghong Han, Kohei Mizuta, Byung M Kang, Michael Bouvet, Norio Yamamoto, Katsuhiro Hayashi, Hiroaki Kimura, Shinji Miwa, Kentaro Igarashi, Takashi Higuchi, Hiroyuki Tsuchiya, Satoru Demura, Robert M Hoffman
{"title":"重组甲硫氨酸酶可协同逆转骨肉瘤细胞对多西他赛的耐药性","authors":"Sei Morinaga, Qinghong Han, Kohei Mizuta, Byung M Kang, Michael Bouvet, Norio Yamamoto, Katsuhiro Hayashi, Hiroaki Kimura, Shinji Miwa, Kentaro Igarashi, Takashi Higuchi, Hiroyuki Tsuchiya, Satoru Demura, Robert M Hoffman","doi":"10.21873/anticanres.17303","DOIUrl":null,"url":null,"abstract":"<p><strong>Background/aim: </strong>Docetaxel combined with gemcitabine is a second-line therapy for osteosarcoma, but its efficacy is limited by the development of docetaxel resistance. The aim of the present study was to determine whether recombinant methioninase (rMETase) could reverse docetaxel resistance developed in osteosarcoma cells.</p><p><strong>Materials and methods: </strong>Docetaxel-resistant 143B (DTR-143B) osteosarcoma cells were established by treating the parental 143B cells to increasing docetaxel concentrations (0.14-24 nM) over 5 months. The 50% inhibitory concentration (IC<sub>50</sub>) of docetaxel and rMETase as well as their combination on human osteosarcoma cells 143B and DTR-143B were determined. Four groups were analysed in vitro: untreated control; docetaxel; rMETase; docetaxel plus rMETase.</p><p><strong>Results: </strong>The IC<sub>50</sub> value of docetaxel for DTR-143B cells was 31.1 nM, compared to 4.38 nM for the parental 143B cells, a 7-fold increase. The combination of rMETase (0.53 U/ml) and docetaxel (4.38 nM) sensitized DTR-143B cells to docetaxel resulting in an inhibition of 73.7% compared to docetaxel alone (7.3%) or rMETase alone (54.6%) (p<0.05). rMETase thus increased the efficacy of docetaxel 10-fold on docetaxel-resistant osteosarcoma cells.</p><p><strong>Conclusion: </strong>rMETase reversed docetaxel resistance of DTR-143B in vitro. The present results indicate the clinical potential of rMETase to overcome docetaxel resistance in osteosarcoma patients.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"44 11","pages":"4773-4778"},"PeriodicalIF":1.6000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Recombinant Methioninase Synergistically Reverses High-docetaxel Resistance Developed in Osteosarcoma Cells.\",\"authors\":\"Sei Morinaga, Qinghong Han, Kohei Mizuta, Byung M Kang, Michael Bouvet, Norio Yamamoto, Katsuhiro Hayashi, Hiroaki Kimura, Shinji Miwa, Kentaro Igarashi, Takashi Higuchi, Hiroyuki Tsuchiya, Satoru Demura, Robert M Hoffman\",\"doi\":\"10.21873/anticanres.17303\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background/aim: </strong>Docetaxel combined with gemcitabine is a second-line therapy for osteosarcoma, but its efficacy is limited by the development of docetaxel resistance. The aim of the present study was to determine whether recombinant methioninase (rMETase) could reverse docetaxel resistance developed in osteosarcoma cells.</p><p><strong>Materials and methods: </strong>Docetaxel-resistant 143B (DTR-143B) osteosarcoma cells were established by treating the parental 143B cells to increasing docetaxel concentrations (0.14-24 nM) over 5 months. The 50% inhibitory concentration (IC<sub>50</sub>) of docetaxel and rMETase as well as their combination on human osteosarcoma cells 143B and DTR-143B were determined. Four groups were analysed in vitro: untreated control; docetaxel; rMETase; docetaxel plus rMETase.</p><p><strong>Results: </strong>The IC<sub>50</sub> value of docetaxel for DTR-143B cells was 31.1 nM, compared to 4.38 nM for the parental 143B cells, a 7-fold increase. The combination of rMETase (0.53 U/ml) and docetaxel (4.38 nM) sensitized DTR-143B cells to docetaxel resulting in an inhibition of 73.7% compared to docetaxel alone (7.3%) or rMETase alone (54.6%) (p<0.05). rMETase thus increased the efficacy of docetaxel 10-fold on docetaxel-resistant osteosarcoma cells.</p><p><strong>Conclusion: </strong>rMETase reversed docetaxel resistance of DTR-143B in vitro. The present results indicate the clinical potential of rMETase to overcome docetaxel resistance in osteosarcoma patients.</p>\",\"PeriodicalId\":8072,\"journal\":{\"name\":\"Anticancer research\",\"volume\":\"44 11\",\"pages\":\"4773-4778\"},\"PeriodicalIF\":1.6000,\"publicationDate\":\"2024-11-01\",\"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.17303\",\"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.17303","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"ONCOLOGY","Score":null,"Total":0}
Recombinant Methioninase Synergistically Reverses High-docetaxel Resistance Developed in Osteosarcoma Cells.
Background/aim: Docetaxel combined with gemcitabine is a second-line therapy for osteosarcoma, but its efficacy is limited by the development of docetaxel resistance. The aim of the present study was to determine whether recombinant methioninase (rMETase) could reverse docetaxel resistance developed in osteosarcoma cells.
Materials and methods: Docetaxel-resistant 143B (DTR-143B) osteosarcoma cells were established by treating the parental 143B cells to increasing docetaxel concentrations (0.14-24 nM) over 5 months. The 50% inhibitory concentration (IC50) of docetaxel and rMETase as well as their combination on human osteosarcoma cells 143B and DTR-143B were determined. Four groups were analysed in vitro: untreated control; docetaxel; rMETase; docetaxel plus rMETase.
Results: The IC50 value of docetaxel for DTR-143B cells was 31.1 nM, compared to 4.38 nM for the parental 143B cells, a 7-fold increase. The combination of rMETase (0.53 U/ml) and docetaxel (4.38 nM) sensitized DTR-143B cells to docetaxel resulting in an inhibition of 73.7% compared to docetaxel alone (7.3%) or rMETase alone (54.6%) (p<0.05). rMETase thus increased the efficacy of docetaxel 10-fold on docetaxel-resistant osteosarcoma cells.
Conclusion: rMETase reversed docetaxel resistance of DTR-143B in vitro. The present results indicate the clinical potential of rMETase to overcome docetaxel resistance in osteosarcoma patients.
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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