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肌醇六磷酸和肌醇可抑制二甲基苯并蒽诱导的大鼠乳腺癌。

Inositol hexaphosphate and inositol inhibit DMBA-induced rat mammary cancer.

作者信息

Vucenik I, Yang G Y, Shamsuddin A M

机构信息

Department of Medical and Research Technology, University of Maryland School of Medicine, Baltimore 21201-1192, USA.

出版信息

Carcinogenesis. 1995 May;16(5):1055-8. doi: 10.1093/carcin/16.5.1055.

Abstract

Because inositol hexaphosphate (InsP6) and inositol (Ins), contained in plants and most mammalian cells, have been demonstrated to have anti-cancer and anti-cell proliferative action in several experimental models of carcinogenesis we have examined the effect of InsP6 +/- Ins on DMBA-induced rat mammary tumor model. Starting two weeks prior to induction with DMBA, the drinking water of female Sprague-Dawley rats was supplemented with either: 15 mM InsP6, 15 mM Ins, or 15 mM InsP6 + 15 mM Ins; a control group received no inositol compounds. Animals (49-day-old) were given a single intragastric dose of DMBA (5 mg/rat) in 1 ml of corn oil administered by oral intubation. After 45 weeks of treatment, the animals in all the three treatment regimens showed a significant reduction (P < 0.05) in tumor incidence. Tumor number, multiplicity and tumor burden were also significantly (P < 0.05) reduced by InsP6 +/- Ins. When all the parameters were taken into consideration, the best results were obtained by the combination treatment of InsP6 + Ins. Four additional groups not receiving DMBA, but drinking tap water, InsP6, Ins, or InsP6 + Ins of the same molarity as experimental groups were observed for the duration of the study to monitor for any toxicity following this long-term treatment; no significant toxicity as evaluated by body weight gain, serum and bone mineral levels was detected. We demonstrate that InsP6 +/- Ins reproducibly inhibits experimental mammary carcinoma, therefore having great potential as a chemopreventive and adjuvant therapeutic agent for this disease as well.

摘要

由于植物和大多数哺乳动物细胞中含有的肌醇六磷酸(InsP6)和肌醇(Ins),已在多种致癌实验模型中被证明具有抗癌和抗细胞增殖作用,因此我们研究了InsP6±Ins对二甲基苯并蒽(DMBA)诱导的大鼠乳腺肿瘤模型的影响。从用DMBA诱导前两周开始,给雌性斯普拉-道利大鼠的饮用水补充以下物质之一:15 mM InsP6、15 mM Ins或15 mM InsP6 + 15 mM Ins;对照组不接受肌醇化合物。给49日龄的动物经口插管灌胃给予1 ml玉米油中含有的单次剂量DMBA(5 mg/大鼠)。治疗45周后,所有三种治疗方案组的动物肿瘤发生率均显著降低(P < 0.05)。InsP6±Ins也显著(P < 0.05)降低了肿瘤数量、多发性和肿瘤负荷。综合考虑所有参数,InsP6 + Ins联合治疗取得了最佳效果。另外观察了四个未接受DMBA但饮用与实验组相同摩尔浓度的自来水、InsP6、Ins或InsP6 + Ins的组,以监测长期治疗后的任何毒性;通过体重增加、血清和骨矿物质水平评估未检测到明显毒性。我们证明InsP6±Ins可重复性地抑制实验性乳腺癌,因此作为该疾病的化学预防和辅助治疗剂也具有巨大潜力。

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