Phenoxodiol protects against Cisplatin induced neurite toxicity in a PC-12 cell model.

Phenoxodiol protects against Cisplatin induced neurite toxicity in a PC-12 cell model.
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DOI:
10.1186/1471-2202-8-61
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发表时间:
2007-08-01
期刊:
影响因子:
2.4
通讯作者:
Turnley AM
Turnley AM
中科院分区:
医学4区
文献类型:
--
作者:
Klein R;Brown D;Turnley AM

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许多常用的化疗药物,例如顺铂,其潜在的抗肿瘤功效因其副作用而受到限制,其中最成问题的问题之一是诱发周围神经病变。尽管已经尝试了许多不同的神经营养、神经保护或抗氧化治疗来预防或治疗神经病,但迄今为止它们所取得的成功有限。 Phenoxodiol 是一种新型化疗药物,对多种癌细胞具有抗增殖和凋亡作用。 PC12 细胞是用于检查神经突生长的常用神经元细胞模型。在这项研究中,我们检查了苯氧二醇是否可以防止顺铂诱导的 PC12 细胞神经突抑制,作为预防神经病变的潜力的指标。使用 PC12 神经元细胞系,选择顺铂浓度,使其在 24 小时内诱导中度或强烈的神经突毒性,但不具有细胞毒性。通过测量神经突生长来评估苯氧二醇对顺铂诱导的神经突毒性的作用。添加100 nM或1 μM的苯氧二醇没有表现出细胞毒性并阻断顺铂诱导的神经突毒性,而10 μM的苯氧二醇具有细胞毒性并增强顺铂的神经突毒性。当添加顺铂24小时,然后洗掉并使细胞恢复48小时时,神经突生长没有恢复,并且苯氧二醇的添加没有进一步促进恢复或恢复顺铂处理的细胞。因此,除了作为化疗剂的潜力外,苯诺二醇还可能与顺铂化疗联合使用,以预防神经病变的诱发。
Many commonly used chemotherapeutic agents, such as Cisplatin, are restricted in their potential anti-neoplastic effectiveness by their side effects, with one of the most problematic being induction of peripheral neuropathy. Although a number of different neurotrophic, neuroprotective or anti-oxidant treatments have been tried in order to prevent or treat the neuropathies, to date they have met with limited success. Phenoxodiol is a new chemotherapeutic agent that has anti-proliferative and apoptotic effects on a range of cancer cells. PC12 cells are a commonly used neuronal cell model for examination of neurite outgrowth. In this study we examined whether phenoxodiol could protect against Cisplatin induced neurite inhibition in PC12 cells as an indication of the potential to protect against neuropathy. Using the PC12 neuronal cell line, concentrations of Cisplatin were chosen that induced moderate or strong neurite toxicity within 24 hrs but were not cytotoxic. The effect of Phenoxodiol on Cisplatin induced neurite toxicity was assessed by measurement of neurite outgrowth. Addition of phenoxodiol at 100 nM or 1 μM showed no cytotoxicity and blocked the Cisplatin induced neurite toxicity, while phenoxodiol at 10 μM was cytotoxic and enhanced neurite toxicity of Cisplatin. When Cisplatin was added for 24 hrs, then washed out and the cells allowed to recover for 48 hrs, neurite outgrowth was not restored and addition of phenoxodiol did not further promote recovery or restore the Cisplatin treated cells. In addition to its potential as a chemotherapeutic agent Phenoxodiol may thus also have the potential to be used in conjunction with Cisplatin chemotherapy to prevent induction of neuropathy.
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