| Objective:2,3-indolinedione (isatine, ISA), also known as Indigo, it is a natural marine antibiotics, was obtained from the marine life lobster and essential to their survival, but also in the traditional Chinese medicine indigo pulverata levis and human endogenous substances. It was the precursors of anti-cancer drugs indirubin. In this paper, 7,12-dimethylbenzanthracene (DMBA) induced rat breast cancer model, the role of ISA in vivo cancer chemoprevention research and explore its anti-cancer mechanism for the development of a cancer chemoprevention in the high efficiency and low toxicity natural active substances.Method:Sprague-Dawley rats were divided into 5 groups:the control group, the model group, the low, medium and high dose group. DMBA were given to induced mammary carcinoma, The occurrence rate of mammary carcinoma was observed, to determination of the weight of the thymus gland, speed, and kidney, the activities of superoxide dismutase (SOD), Glutathione peroxidase (GSH-px), Malondialdhyde (MDA) and the tumor necrosis factor(TNF-α) in blood serum. The proliferation cell nuclear antigen (PCNA) assayed by immunohistochemical S-P method, HE staining was used to examine the tumors.Result:1. The weight in the model group compared with the control group decreased after the ninth week (p<0.05), while the body weight in the low, medium and high ISA dose groups decreased, compared with the control group no difference (p>0.05), at week 9, the low, medium dose group compared with the model group weight (p<0.05), in the week 16,12 there is no difference (p>0.05);2. the model group were given DMBA, on the ninten week the mass were reached, while the treatment group delayed to the 12th week; about the tumor incidence, the low, medium and high ISA dose groups were lower than the Model control group, of which there was significant difference between the low dose group and model control group (P<0.05);3. As compared with control group, the index of spleen and thymus in the model group were decreased slightly (P<0.05), meanwhile, the index of the spleen in the low and middle group and the index of thymus of the high group were increased significantly as the model group (P <0.05), there were no significant difference in the five groups of the index of kidney(p>0.05); 4. Moreover, the activities of GSH-px and SOD significantly decreased (P<0.05) in the modelgroup compared with the control group, while the GSH-px in the low and high group and the activities of the SOD in the low and middle group was increased significantly (P<0.05) compared with the model group;5. The contend of TNF-ain the model group were higher than the control group significantly (P<0.05), while the low and high group were lower than the model group(P<0.05). Compared with model group, the percentage of positive cells of PCNA in the low, middle dose group decreased significantly (p<0.05). Histopathology showed that all the groups of the rats baered breast cancer.Conclusion:These results suggested that the ISA can delay the occurrence of DMBA-induced mammary tumors, reduce the incidence of mammary carcinoma, strengthen the immune system of the tumor-bearing rats, Clear the free radical oxygen produced by oxidative stress, and proliferation inhibition of carcinoma cell lines as well, reduce the expression of the PCNA in tumors. So that the ISA might is a novel agent of potentially chemopreventive affection on mammary carcinoma produced by DMBA in rats. |
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