【作者】 王瑞；

【导师】 陆士新； 王瑞林；

【作者基本信息】 郑州大学 ， 病理学与病理生理学， 2006， 博士

【摘要】 化疗是目前恶性肿瘤治疗的主要手段之一，然而多数化疗药物在杀伤肿瘤细胞的同时，对正常人体细胞也有较大损伤，产生毒副反应，从而使化疗不能顺利进行，严重影响了疗效。寻找和发现能够增加肿瘤对化疗药物敏感性的化疗增敏剂，使化疗药物能更大程度的提高疗效并减少毒副反应，是治疗恶性肿瘤急需解决的问题。 胰岛素是一种代谢促进剂，可以提高细胞和组织的代谢水平。另一方面，它还可以促进RNA和DNA的合成，刺激正常细胞和肿瘤细胞的生长增殖，诱导肿瘤细胞进入增殖周期。已被证实：生长缓慢，生长分数低的肿瘤对化疗敏感性差；而生长快，生长分数高的肿瘤却有较好的化疗敏感性。生长快的肿瘤细胞多处于增殖周期，分裂增殖活跃，代谢旺盛，对化疗药物敏感；而生长缓慢的恶性肿瘤较多的肿瘤细胞处于非增殖周期，受细胞毒药物的影响也较小。 合理地使用促代谢剂胰岛素，将肿瘤细胞调整到代谢旺盛，分裂增殖活跃的状态，能够增加肿瘤组织对化疗药物的敏感性。本实验证实：裸鼠移植瘤动物模型上，胰岛素可增强5-氟尿嘧啶(5-FU)的化疗效果。增效的过程毒性并不增加。这与以往的体外研究结果一致。在观察疗效的基础上，对胰岛素增效机制也做了进一步探讨。 第一部分 胰岛素对化疗药物5-氟尿嘧啶的增效作用研究方法： (1) 建立裸鼠S180肉瘤、H22肝癌和人食管癌移植瘤动物模型，随机分为六组：对照组、单用胰岛素组、单用5-FU组、大中小剂量胰岛素联合5-FU组。胰岛素三种剂量分别按0.09，0.06，0.03U／20g左腋皮下注射，5-FU按10mg／kg腹腔注射，胰岛素提前5-FU 30分钟给药。为防止低血糖的发生，每只裸鼠按0.8ml／20g灌胃50％G-S。更多还原

【Abstract】 Chemotherapy is one of the main ways to treat malignant tumor currently, but many chemotherapeutic drugs damage normal cells with side effects when they kill cancer cells. Chemotherapy can’t be done smoothly and clinical efficacy is poor. So it is very important to find chemosensitizers which improve the sensitivity of chemotherapeutic drugs and reduce side effects.Insulin is one metabolism accelerant. It can improve the metabolic level of cell and tissue. In addition, it can promote the synthesis of RNA and DNA, stimulate the growth of normal and cancer cells and induce cancer cells into the cycle of multiplication. It is known that slowly growing cancers with a low-growth fraction are less sensitive to chemotherapy, whereas rapidly growing tumors with high-growth fractions are more sensitive to chemotherapy. One of the main reasons is that rapidly growing cancers have higher metabolism level than slowly growing cancers and cancer cells in higher metabolism status are more subject to be attacked by chemotherapy drugs.Insulin was used properly as accelerant to modulate tumor cells into the state of high metabolism and active multiplication, which makes cancer tissue more sensitive to chemotherapeutic drugs. This study has demonstrated insulin can enhance the chemotherapeutic effect of 5-FU on nude mice transplanted tumor animal model without increasing toxicity. The result was in agreement with the previous study in vitro. In addition, the enhancement mechanism of insulin on 5-FU was also explored further.更多还原