BENEFICIAL EFFECTS OF GINKGO BILOBA IN CANCER

描述（申请人摘要）：尽管我们对癌症的理解 虽然进展迅速，但它仍然是死亡的主要原因， 美国，心脏病之后。全球死亡人数的增加 从恶性肿瘤一起失败的所有"灵丹妙药" 预防和/或治疗这些疾病的方法使我们回顾 药材银杏是最古老的树种之一， 已经被用于传统医学几百年了 年我们过去十年的研究重点是了解 外周型苯二氮卓受体（PBR）的功能， 参与细胞内胆固醇区室化的蛋白。PBR 在侵袭性人乳腺癌细胞中表达显著增加 其中其表达与增加的细胞增殖相关， 细胞的侵袭性表型。在初步研究中，我们观察到， 银杏叶标准提取物（EGB 761）抑制PBR表达 和侵袭性人乳腺肿瘤细胞系MDA-231中的细胞增殖， 但在非侵袭性细胞系中没有。利用我们发现的基因表达阵列 EGB 761处理调节特定基因产物的表达， 包括癌基因、细胞周期调节因子、前列腺增生相关产物， 转录因子和生长因子，参与各种途径 调节细胞增殖。这些体外数据在体内试验中得到了验证。 EGB 761处理显著抑制生长和PBR的模型 MDA-231细胞裸鼠移植瘤的表达。综合来看，这些数据 提示EGB 761可能具有抑制细胞生长特性。我们假设 EGB 761的细胞抑制作用不限于MDA-231细胞， 也适用于其他致癌肿瘤细胞。我们的首要目标是 通过检查EGB 761对其他侵袭性疾病的影响来验证这些发现。 乳腺癌细胞系。EGB 761对细胞增殖的影响， 将在体外研究细胞凋亡、细胞周期和基因表达。的影响 原发肿瘤大小、肿瘤中转移灶和血管形成的存在 将在细胞异种移植裸鼠模型中进行体内研究。考虑 PBR也在诸如神经胶质瘤、肝细胞瘤、结肠癌和结肠癌的癌症中过表达。 我们的第二个目的是检查EGB 761对前列腺癌的作用， 调节体外和体内增殖和生长速率， 分别对胶质瘤、肝癌、结肠癌和前列腺癌细胞。这些 实验应证明EGB 761是否可用于预防和/或 稳定癌症的发展。

DESCRIPTION (APPLICANT'S ABSTRACT): Although our understanding of cancer has dramatically progressed, it still remains the leading cause of death, in the United States, after heart disease. The worldwide increased number of deaths from malignant tumors together with the failure of all "magic bullets" developed to prevent and/or cure these diseases brought us to look back at medicinal herbs. Ginkgo biloba is one of the most ancient trees and extracts from its leaves have been used in traditional medicine for several hundred years. Our research for the last decade has focused on understanding the function of the peripheral-type benzodiazepine receptor (PBR), an ubiquitous protein involved in intracellular cholesterol compartmentalization. PBR expression is dramatically increased in aggressive human breast cancer cells where its expression correlates with the increased cell proliferation and the aggressive phenotype of the cells. In preliminary studies we observed that the standardized extract o Ginkgo biloba leaves (EGB 761) inhibited PBR expression and cell proliferation in the aggressive human breast tumor cell line MDA-23 1, but not in a non-aggressive cell line. Using a gene expression array we found that EGB 761 treatment regulated the expression of specific gene products, including oncogenes, cell cycle regulators, apoptosis-related products, transcription factors, and growth factors, involved in various pathways regulating cell proliferation. These in vitro data were validated in an in vivo model where treatment with EGB 761 significantly inhibited the growth and PBR expression of MDA-231 cell xenografts in nude mice. Taken together, these data suggest that EGB 761 may exert cytostatic properties. It is our hypothesis that the cytostatic effect of EGB 761 is not confined to the MDA-231 cells but applies to other carcinogenic tumor cells. Our first specific aim is to validate these findings by examining the effect of EGB 761 on other aggressive breast cancer cell lines. The effect of EGB 761 on cell proliferation, apoptosis, cell cycle and gene expression will be studied in vitro. Its effect on primary tumor size, presence of metastases and vascularization in the tumor area will be studied in vivo in a cell xenograft nude mice model. Considering that PBR is also overexpressed in cancers such as gliomas, hepatomas, colon and prostatic carcinomas, our second aim is to examine the effects of EGB 761 on regulating the in vitro and in vivo proliferation and growth rates, respectively, of glioma, hepatoma, colon and prostatic carcinoma cells. These experiments should demonstrate if EGB 761 could be used to prevent and/or stabilize the progression of cancer.