【作者】 李铭；

【导师】 蔡文清；

【作者基本信息】 河北医科大学 ， 外科学， 2006， 博士

【摘要】 目前泌尿系统恶性肿瘤尤其是进展期肿瘤缺乏有效的药物治疗。膀胱癌是泌尿系统中发病率最高的恶性肿瘤,且极易复发,肾癌和前列腺癌出现症状时多已是较为晚期,预后差,对大多数的一线化疗药物的反应极差。恶性肿瘤对一般化疗药物敏感性低的主要原因是不同生物学特性的肿瘤对这些药物有着天然的及获得的抗药性,单一的治疗常不能控制其发展,因此非常需要更多的可选择药物,尤其是低毒高效的中药提取物,是目前世界上肿瘤治疗的发展趋势,也是我们研究的重要课题。目前很多从植物中提取的生物碱在肿瘤防治方面具有重要作用,如羟基喜树碱、紫杉醇等已经广泛应用于肝癌、膀胱癌等恶性肿瘤的治疗中,通过影响DNA合成、诱导凋亡和细胞毒作用发挥抗肿瘤作用,取得了良好的疗效,并且没有交叉耐药。中药北豆根( Menispermum dauricum DC)一般常用于抑菌、降血压、抗心律失常等治疗。最近我们发现少数有关北豆根的提取物蝙蝠葛酚性碱(Phenolic alkaloids of menispermum dauricum,PAMD)有抗鼻咽癌和白血病作用的报道,那么同样是生物碱,PAMD是否会有与羟基喜树碱相似或更好的效果?目前仍未见到有关此药对泌尿系统恶性肿瘤作用研究的报道。本实验针对性的选择泌尿系统肿瘤,观察北豆根粗提物蝙蝠葛酚性碱和纯品蝙蝠葛碱(Dauricine,Dau)对膀胱移行细胞癌T-24细胞株、肾癌786-0细胞株、前列腺癌PC-3细胞株及原代培养细胞体内外抗肿瘤作用、抗突变作用、免疫调节作用及其抗肿瘤机制,目的是为抗肿瘤新药开发、研制提供科学依据,尤其为泌尿系统肿瘤的治疗提供理论依据。第一部分PAMD及其纯化物Dau对人泌尿系统恶性肿瘤增殖抑制作用的研究。目的:观察PAMD及其纯化物Dau对膀胱移行细胞癌T-24细胞株、肾癌786-0细胞株、前列腺癌PC-3细胞株原代肾癌和膀胱癌细胞体外抗肿瘤作用。方法:更多还原

【Abstract】 Up to now, malignant tumors of urinary system are lack of effective drug treatment,especially for those in advanced stage. The morbidity of bladder carcinoma is maximal compared with other malignant tumours in urinary system,furthermore, bladder carcinoma is extremely easy to recur, As for renal cell carcinoma and prostatic carcinoma,symptoms appearance offen means fairly advanced stage. These cancers are often insensitive to chemotherapeutics commonly used in clinic, Prognosis is bad.Why do so many cancers resist to general drugs? One of the main reasons is that carcinomas with different biological characteristics possess natural and acquired drug resistance. Simple administration could not control disease effectively,so more new drugs or approaches are needed for us to select,especially those low-poisonous and high-performance agentias,such as traditional Chinese medicine. Extracting active component from herbs is tumor therapeutic tendency in the world. It’s also our important subject to study.Many alkaloid from plants have important value in treatment and prevention of tumour. For instance,hydroxycamptothecine and paclitaxel have been widely used for treating liver cancer,bladder cancer and many other malignant carcinomas. Curative effects were satisfactory, moreover , there is no crossing drug-resistance.The mechanism of anti-tumor include controlling DNA synthesis, inducing apoptosis and cell toxic action.Asiatic moonseed rhizome,the traditional Chinese medicine, has bacteriostasis and blood pressure controlling efficacy. It also has effect against cardiac arrhythmia. Recently extracts of Menispermum dauricum were discovered to be anti-tumor effects, named Phenolic alkaloids of menispermum dauricum(PAMD)which can inhibit nasopharyngeal carcinoma更多还原