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目的:东莨菪亭(7-羟基-6-甲氧基香豆素)是从常绿钩吻中提取的有效成分,前期体外研究证实了其抗肿瘤潜能,本研究评价其在小鼠体内的抗肿瘤作用。方法:30只健康小鼠随机分为正常对照组、模型组、溶剂对照组和低、高剂量东莨菪亭组,每组6只。正常对照组小鼠不接受任何干预,其余小鼠背部涂抹100μg 7 ,12-二甲基苯并蒽(7 ,12-di methylbenz[a]anthra-cene ,DMBA)(每周一次)和1 %巴豆油(每周2次)诱导皮肤乳头状瘤,共24周。溶剂组小鼠在造模基础上每天予2 %酒精口服,低剂量(50 mg/kg)和高剂量(100 mg/kg)东莨菪亭组小鼠每天予东莨菪亭治疗。治疗24周后,检测碱性磷酸酶、超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶和谷胱甘肽S-转移酶活性;信号蛋白及其受体,包括芳香烃受体(Aryl hydrocarbon receptor , AhR)、p53、细胞色素P450亚酶1A1(cytochrome P450 1A1 , CYP1A1)、增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)、信号转导和转录激活因子3(signal transducer and activator of transcription-3 ,Stat-3)、存活素、金属基质蛋白酶2、cyclin D1、c-myc、金属蛋白酶组织抑制因子2和半胱氨酸蛋白酶3(caspase-3) ,采用逆转录聚合酶链反应、蛋白印迹法或免疫沉淀法检测。结果:致癌物DMBA和巴豆油可以诱导毒性反应,生化指标中相关酶活性升高,AhR、CYP1A1、PCNA、Stat-3、存活素、MMP-2、cyclin D1和c-myc表达上调,p53、caspase-3和TI MP-2表达下调。荷瘤小鼠采用东莨菪亭治疗后,生化指标中相关酶的活性下降,蛋白表达和毒性生物标志物恢复正常。结论:东莨菪亭可能通过下调AhR表达来下调一些重要信号蛋白的表达,其作用机制可能是通过竞争性抑制存活素的表达。分裂原活化蛋白激酶可能也起到关键作用。东莨菪亭或许可作为化疗的替代药物用于治疗肿瘤。
OBJECTIVE: Toad (7-Hydroxy-6-methoxycoumarin) is an effective ingredient extracted from the evergreen hookfish, and its in vitro studies have confirmed its antitumor potential. This study evaluated its effect in mice. Anti-tumor effect. Methods: Thirty healthy mice were randomly divided into normal control group, model group, vehicle control group, and low-dose high-dose Dongzhiting group, with 6 rats in each group. The mice in the normal control group received no intervention and the remaining mice were smeared with 100 μg of 7, 12-dimethylbenz[a]anthra-cene (DMBA) (once a week) and 1% on the back. Croton oil (twice a week) induces papilloma of the skin for a total of 24 weeks. The mice in the solvent group were given 2% alcohol per day on a model basis. The mice in the low-dose (50 mg/kg) and high-dose (100 mg/kg) scopoletin groups were treated with Dongzhiting daily. After 24 weeks of treatment, alkaline phosphatase, superoxide dismutase, catalase, glutathione peroxidase, and glutathione S-transferase activity were detected; signaling proteins and their receptors, including aroma Aryl hydrocarbon receptor (AhR), p53, cytochrome P450 1A1 (CYP1A1), proliferating cell nuclear antigen (PCNA), signal transduction and transcription activator 3 (signal transducer) And activator of transcription-3, Stat-3), survivin, metal matrix protease 2, cyclin D1, c-myc, tissue inhibitor of metalloproteinase 2 and caspase-3, using reverse transcription polymerization Enzyme chain reaction, Western blot or immunoprecipitation assay. RESULTS: Carcinogens DMBA and Croton oil induced toxicity, increased biochemical activity of related enzymes, increased expression of AhR, CYP1A1, PCNA, Stat-3, survivin, MMP-2, cyclin D1 and c-myc, p53, The expression of caspase-3 and TI MP-2 was down-regulated. After tumor-bearing mice were treated with scopoletin, the activity of related enzymes in biochemical markers decreased, and protein expression and biomarkers of toxicity returned to normal. Conclusion: Dongqinting may down-regulate the expression of some important signal proteins by down-regulating the expression of AhR. Its mechanism may be through the competitive inhibition of survivin expression. Mitogen-activated protein kinases may also play a key role. Dongqianting may be licensed as an alternative to chemotherapy for the treatment of tumors.