Oral administration of an estrogen metabolite-induced potentiation of radiation antitumor effects in presence of wild-type p53 in non-small-cell lung cancer
Oral administration of an estrogen metabolite-induced potentiation of radiation antitumor effects in presence of wild-type p53 in non-small-cell lung cancer
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DOI：
10.1016/s0360-3016(00)00767-7
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发表时间：
2000-11-01
影响因子：
7
通讯作者：
Mukhopadhyay, T
中科院分区：
文献类型：
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作者：
Huober, JB;Nakamura, S;Mukhopadhyay, T
目的：探讨2-甲氧雌酮作为抗肿瘤和放射增敏剂治疗人类恶性肿瘤的疗效。方法和材料：首先将两种p53野生型癌细胞系暴露于辐射下，然后口服一种无毒代谢物2-甲氧基雌二醇（2ME）制剂，以稳定p53水平。结果:通过G1生长和凋亡抑制细胞生长，随后的体外生长和Tunel实验表明，该组合在诱导p53蛋白积累、稳定p53蛋白水平、大幅降低肿瘤细胞体外长期生长（约80%）和集落形成（约95%）以及诱导细胞凋亡方面优于单独放疗。然而，携带突变p53的H322细胞系对该治疗方案相对不敏感。Western blot分析显示，生长抑制与p53和p21蛋白积累水平升高有关。nu/nu小鼠皮下肿瘤实验表明，联合治疗在减少肿瘤生长方面优于单独放疗（与单独放疗相比，减少了50%）。结论：因此，我们的研究证实了一种独特的策略，即口服无毒雌激素代谢物2ME，可显著增强对皮下肿瘤的辐射效应，且无任何毒性，这表明该策略可能在临床上作为辅助治疗有用。(C) 2000 Elsevier Science Inc.；
Purpose: The purpose of this study was to investigate the efficacy of 2-methosyestradiol as an antitumor and radiosensitizing agent for the treatment of human malignancy.Methods and Materials: Two cancer cell lines with wild-type p53 status were exposed first to irradiation and then to an oral formulation of the nontoxic metabolite 2-methoxyestradiol (2ME) to stabilize p53 levels.Results: Cell growth was inhibited via G1 growth and apoptosis, Subsequent irt vitro growth and Tunel assays indicated that this combination was superior to radiation alone at inducing p53 protein accumulation, stabilizing p53 protein levels, and substantially reducing long-term tumor cell growth (similar to 80%) and colony formation (similar to 95%) in vitro, and inducing apoptosis, However, harboring mutated p53, H322 cell line, was relatively insensitive to such a treatment regimen, Western blot analysis revealed that growth inhibition was associated with increased levels of p53 and p21 protein accumulation. Experiments with subcutaneous tumor in a nu/nu mouse showed the combination treatment to be superior to radiation alone at reducing tumor growth (similar to 50% reduction as compared to radiation alone) in vivo.Conclusion: Thus, our studies confirmed a unique strategy whereby oral administration of a nontoxic estrogen metabolite, 2ME, significantly enhanced the radiation effect on a subcutaneous tumor without any toxicity and suggesting that this strategy mag be clinically useful as an adjuvant therapy. (C) 2000 Elsevier Science Inc.