前列腺癌血管生成机制和木犀草素对前列腺癌抑制作用研究
文献类型：学位论文
| 作者 | 周琼 |
| 学位类别 | 博士 |
| 答辩日期 | 2008-06 |
| 授予单位 | 中国科学院上海生命科学研究院营养科学研究所 |
| 授予地点 | 中国科学院上海生命科学研究院 |
| 导师 | 方靖 |
| 关键词 | 前列腺癌 木犀草素 IGF-1R E-cadherin 生长 侵袭 |
| 其他题名 | The mechanism of reactive oxygen species on insulin-induced prostate cancer angiogenesis and the investigation of luteolin on proliferation and invasion of prostate cancer cells |
| 学位专业 | 生物化学与分子生物学 |
| 中文摘要 | 前列腺癌是目前导致西方国家男性死亡的主要疾病之一，在我国前列腺癌发病率病上升非常迅速。由于我国人口基数大，前列腺癌患病人数激增，必须重视前列腺癌的预防和治疗。前列腺癌是一种非常复杂的疾病，病因尚不完全清楚，可能与遗传、环境、性激素等多种因素有关。前列腺癌的传统治疗方法包括手术、放化疗，治疗效果并不十分理想。手术治疗后复发率比较高，一般复发的前列腺癌转变为雄激素非依赖的，治疗更为困难。因此，弄清前列腺癌的发病机理，积极开展前列腺癌的预防是对付这种疾病的更明智的态度和方法。 该论文主要由两个大部分组成：第一部分（第一章）为胰岛素通过活性氧对前列腺癌细胞诱导的血管生成的机制研究。流行病学调查显示高胰岛素（hyperinsulinaemia）是引起前列腺癌发病的危险因素之一，同时高胰岛素也与前列腺癌复发有密切关系，但是其分子机理尚不清楚。前列腺癌的发展是一个非常复杂的过程，其中血管生成起非常重要的作用。我们研究发现，在前列腺癌细胞中，胰岛素能诱导产生过氧化氢，而胰岛素诱导生成的过氧化氢能促进HIF¬¬-1α和VEGF的表达，从而促进肿瘤的血管生成。这一研究结果有助于了解前列腺癌复杂的发病机理，为预防和治疗前列腺癌提供理论依据。第二部分主要为木犀草素对前列腺癌的抑制，包括两个方面（第二章和第三章）：一是木犀草素对前列腺癌细胞生长的抑制；二是木犀草素对前列腺癌细胞侵袭和转移的抑制。木犀草素是一种植物来源的黄酮类化合物，属天然抗氧化剂。其来源广泛，毒副作用小，适合用来进行肿瘤的化学预防。我们的研究发现，木犀草素能通过对IGF-1R信号的抑制来抑制前列腺癌细胞的生长，同时还能通过上调E-cadherin的表达来抑制前列腺癌细胞的侵袭和转移，具有发展成为前列腺癌化学预防药物的潜力。 |
| 索取号 | D2008-156 |
| 英文摘要 | Prostate cancer is one of leading cause of death in male in western countries. In our country, the incidence of prostate cancer increases very rapidliy recently. Due to the huge population number of our county, the absolute number of prostate cancer patients will be very big. Prostate cancer is a very complicated disease. The pathogeny is not very clear until now. It is related to genetic factors, environment, and sexual hormone. The results of traditional therapy, including operation surgery, radiation and chemotherapy, are not satisfying. The rate of recurrence is pretty high and most recurrent prostate cancer progress into androgen-independent stage, which is more difficult to cure. So it is imortant to elucidate the cause of prosate cancer and take action in prevention of prostate cancer. My work is consisted of two parts. The first part is the study on the mechanisms that insulin induces angiogenesis of prostate cancer. Epidemiological studies demonstrated that hyperinsulinaemia is an important risk factor of prostate cancer development and recurrence. However, the molecular mechanism is still unknown. The progression of prostate cancer development is very complicated and angiogenesis plays a critical role in it. Angiogenesis is indispensable for tumor growth and metastasis. In our study, we demonstrated that insulin stimulated hydrogen peroxide (H2O2) production in prostate cancer cell PC¬¬-3. Insulin-induced H2O2 is critical for the insulin-induced expression of HIF-1α /VEGF and stimulation of prostate cancer’s angiogenesis. These results are helpful to understand the mechanisms of prostate cancer development and may provide some useful information for prostate cancer prevention and therapy in the future. The second part of my work is the investigation of luteolin against prostate cancer.In this part, we demonstrate that (1) luteolin inhibits proliferation of prosate cancer cells through IGF-1/IGF-1R pathway, and (2) luteolin inhibits invasion of prostate cancer cells via E-cadherin. Luteolin is a widely distributed flavonoid and has little toxicity. So, it is quite suitable for cancer chemoprevention. Our results uncover the possible mechanisms that luteolin inhibits human prostate cancers, and suggest that luteolin is a potent agent for future chemoprevention and chemotheraputics of prostate cancer. |
| 语种 | 中文 |
| 公开日期 | 2015-12-24 |
| 源URL | [http://202.127.25.144/handle/331004/377]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所_营养与癌症研究组 |
| 推荐引用方式 GB/T 7714 | 周琼. 前列腺癌血管生成机制和木犀草素对前列腺癌抑制作用研究[D]. 中国科学院上海生命科学研究院. 中国科学院上海生命科学研究院营养科学研究所. 2008. |
入库方式： OAI收割
来源：上海营养与健康研究所
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