Recombinant Methioninase Synergistically Reverses High-docetaxel Resistance Developed in Osteosarcoma Cells.

IF 1.6 4区医学 Q4 ONCOLOGY

Anticancer research Pub Date : 2024-11-01 DOI:10.21873/anticanres.17303

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

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引用次数: 0

Abstract

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.

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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

背景/目的：多西他赛联合吉西他滨是骨肉瘤的二线疗法，但其疗效因多西他赛耐药性的产生而受到限制。本研究旨在确定重组甲硫氨酸酶（rMETase）能否逆转骨肉瘤细胞产生的多西他赛耐药性：多西他赛耐药的143B（DTR-143B）骨肉瘤细胞是通过对亲代143B细胞进行为期5个月的多西他赛浓度（0.14-24 nM）递增处理而建立的。测定了多西他赛和 rMETase 及其组合对人骨肉瘤细胞 143B 和 DTR-143B 的 50% 抑制浓度（IC50）。体外分析分为四组：未处理对照组；多西他赛组；rMETase 组；多西他赛加 rMETase 组：结果：多西他赛对 DTR-143B 细胞的 IC50 值为 31.1 nM，而对亲本 143B 细胞的 IC50 值为 4.38 nM，增加了 7 倍。rMET酶（0.53 U/ml）和多西他赛（4.38 nM）的组合使DTR-143B细胞对多西他赛敏感，与单独使用多西他赛（7.3%）或单独使用rMET酶（54.6%）相比，抑制率达到73.7%（p结论：rMET酶在体外逆转了DTR-143B对多西他赛的耐药性。本研究结果表明，rMETase 具有克服骨肉瘤患者多西他赛耐药性的临床潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Anticancer research 医学-肿瘤学

CiteScore

3.70

自引率

10.00%

发文量

566

审稿时长

2 months

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.