β -葡聚糖(舞茸多糖)诱导人前列腺癌细胞凋亡的研究。

Molecular urology Pub Date : 2000-01-01
S A Fullerton, A A Samadi, D G Tortorelis, M S Choudhury, C Mallouh, H Tazaki, S Konno
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引用次数: 0

摘要

目的:为探索激素难治性前列腺癌更有效的治疗方法,研究灰茸多糖β -葡聚糖对前列腺癌细胞的体外抗肿瘤作用。材料和方法:用不同浓度的高纯度β -葡聚糖制剂Grifron-D(R) (GD)处理人前列腺癌PC-3细胞,24 h检测细胞活力,并通过脂质过氧化(LPO)实验和原位杂交(ISH)方法揭示GD的抗肿瘤机制。结果:一项剂量反应研究表明,当GD >或= 480微克/毫升时,24小时内几乎完全(>95%)细胞死亡。30 ~ 60微克/毫升的GD与200微克/毫升的维生素C联合使用,与单独使用480微克/毫升的GD一样有效,诱导>90%的细胞毒性死亡。与各种抗癌药物同时使用,除卡莫司汀/GD联合使用外,其疗效几乎没有增强(细胞活力降低约90%)。gd处理的细胞LPO水平显著(两倍)升高,ISH染色呈阳性,表明氧化膜损伤导致细胞凋亡。结论:灰树菇中的生物活性β -葡聚糖可能通过氧化应激对体外前列腺癌细胞具有细胞毒作用,导致细胞凋亡。维生素C增强GD的作用和GD对carmustine的化学增敏作用也可能具有临床意义。因此,这种独特的蘑菇多糖可能有很大的潜力作为前列腺癌的替代治疗方式。
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Induction of apoptosis in human prostatic cancer cells with beta-glucan (Maitake mushroom polysaccharide).

Purpose: To explore more effective treatment for hormone-refractory prostate cancer, we investigated the potential antitumor effect of beta-glucan, a polysaccharide of the Maitake mushroom, on prostatic cancer cells in vitro.

Materials and methods: Human prostate cancer PC-3 cells were treated with various concentrations of the highly purified beta-glucan preparation Grifron-D(R) (GD), and viability was determined at 24 h. Lipid peroxidation (LPO) assay and in situ hybridization (ISH) were performed to unravel the antitumor mechanism of GD.

Results: A dose-response study showed that almost complete (>95%) cell death was attained in 24 h with GD > or = 480 microg/mL. Combinations of GD in a concentration as low as 30 to 60 microg/mL with 200 microM vitamin C were as effective as GD alone at 480 microg/mL, inducing >90% cytotoxic cell death. Simultaneous use with various anticancer drugs showed little potentiation of their efficacy except for the carmustine/GD combination (approximately 90% reduction in cell viability). The significantly (twofold) elevated LPO level and positive ISH staining of GD-treated cells indicated oxidative membrane damage resulting in apoptotic cell death.

Conclusion: A bioactive beta-glucan from the Maitake mushroom has a cytotoxic effect, presumably through oxidative stress, on prostatic cancer cells in vitro, leading to apoptosis. Potentiation of GD action by vitamin C and the chemosensitizing effect of GD on carmustine may also have clinical implications. Therefore, this unique mushroom polysaccharide may have great a potential as an alternative therapeutic modality for prostate cancer.

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