论文总字数：23847字

摘 要

如今，癌症已经成为我国人口死亡的主要原因之一，其中，卵巢癌在妇科肿瘤中占第三位，由于卵巢癌发病隐匿，发病机制尚不清楚，对治疗卵巢癌构成了一大难题。霉酚酸酯（MMF）具有独特的免疫抑制作用和较高的安全性，作为前药，口服后能够迅速水解为活性代谢产物霉酚酸（MPA）， 抑制机体细胞嘌呤核苷酸从头合成途径中的限速酶肌苷—磷酸脱氢酶Ⅱ的活性，抑制T和B淋巴细胞的增殖反应，从而达到抗肿瘤效果。

本研究是通过建立小鼠的抗肿瘤模型，即对小鼠进行异种移植卵巢癌细胞使其在小鼠身上生长繁殖，再将霉酚酸酯药物注入小鼠体内，观察并记录卵巢癌细胞的变化情况。结果：MPA及其修饰物能够有效抑制A2780细胞的增殖，且成剂量依赖性关系。霉酚酸在A2780细胞上的半数抑制浓度IC₅₀为1.6μM，最高剂量300μM抑制率在89%左右。霉酚酸衍生物M1在A2780细胞上的半数抑制浓度IC₅₀为20μM。M2在A2780细胞上的半数抑制浓度IC₅₀为5μM。M3在A2780细胞上的半数抑制浓度IC₅₀为4μM，最高剂量300μM抑制率在89%左右。进一步的体内抗肿瘤活性检测表明，MPA抗卵巢癌效果显著。

关键词：卵巢癌 免疫抑制剂 霉酚酸酯 霉酚酸 抗肿瘤

Efficacy studies of ovarian cancer and anti-modified objects within the MPA

Abstract

Cancer has become the leading cause of death in our country, ovarian cancer accounts for third place in gynecological tumors, ovarian cancer because the occult, the pathogenesis is unclear, it is already advanced when diagnosed.And mycophenolate mofetil (MMF) with unique immunosuppressive activity and high safety, as the prodrug is rapidly hydrolyzed in vivo after oral administration of the active metabolite mycophenolic acid (MPA), reversible inhibition of the body's efficient cell selection de novo synthesis of purine nucleotides in the rate-limiting enzyme inosine - ⅱ phosphate dehydrogenase activity, inhibition of proliferation of T and B lymphocytes, to achieve the anti-tumor effect.

In this study, through the establishment of anti-tumor model in mice, that ovarian cancer xenograft mice so that growth and reproduction in mice,then injected the drug mycophenolate mice were observed and recorded ovarian cancer changes.The results: MPA and modifications can effectively inhibit the proliferation of A2780 cells, and a dose-dependent manner.

Mycophenolic acid on A2780 cells the IC50 of 1.6μM, the highest dose of 300μM inhibition rate of around 89%. Mycophenolic acid derivatives M1 on A2780 cells to IC50 of 20μM. M2 A2780 cells in the half inhibition concentration IC50 was 5μM. M3 A2780 cells in the half inhibition concentration IC50 of 4μM, 300μM highest dose rate of about 89% inhibition. Further testing showed anti-tumor activity in vivo, MPA significant effect against ovarian cancer.

Keywords:Ovarian Cancer; Immunosuppressive drugs; Mycophenolate mofetil; Mycophenolic acid;Anti-tumor

目 录

摘要·····················································Ⅰ

ABSTRACT··············································Ⅱ

第一章 研究背景···········································1

1.1卵巢癌的现状 ···············································1

1.1.1卵巢癌的病发、死亡情况·································1

1.1.2卵巢癌的病因···········································1

1.1.3卵巢癌的临床表现·······································2

1.1.4卵巢癌临床治疗方法·····································2

1.2 免疫抑制剂··················································2

1.2.1免疫抑制剂介绍·········································2

1.2.2免疫抑制剂分类.········································3

1.2.3抗肿瘤活性的免疫抑制剂.···································4

1.3 MPA的药物介绍··············································5

1.3.1 MPA的简介·············································5

1.3.2 MPA的作用机制·········································5

1.3.3 MPA的临床应用········································6

1.3.4 MPA的作用机制········································7

第二章 实验部分···········································8

2.1引言 ·······················································8

2.2实验材料和方法··············································8

2.2.1 实验准备··············································8

2.2.2 实验试剂··············································9

2.2.3 实验仪器··············································11

2.3 MPA以及其衍生物的配制······································11

2.3.1 细胞实验的药物配制····································11

2.3.2 动物实验的药物配制····································11

2.4 MPA及其衍生物的体外活性检测实验····························11

2.4.1 A2780细胞培养········································12

2.4.2 A2780细胞的MPA以及其衍生物的敏感实验················12

2.5 MPA及其衍生物的体内活性检测实验····························12

2.5.1 裸鼠的养殖············································12

2.5.2 裸鼠的荷瘤建立动物模型································14

2.5.3 实验观察和记录········································14

2.5.4 实验终止·············································14

2.6 实验结果与讨论·············································14

2.6.1 MPA及其衍生物的体外活性检测·························15

2.6.2 MPA及其衍生物的体内活性检测·························15

2.7 实验结论···················································18

2.8 课题展望···················································18

参考文献·················································20致谢·····················································22

第一章 研究背景

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