Pretner Ewald, Amri Hakima, Li Wenping, Brown Rachel, Lin Chin-Shoou, Makariou Erini, Defeudis Francis V, Drieu Katy, Papadopoulos Vassilios
Department of Biochemistry and Molecular Biology, Georgetown University School of Medicine, Washington DC, 20007, USA.
Anticancer Res. 2006 Jan-Feb;26(1A):9-22.
The peripheral-type benzodiazepine receptor (PBR) is an 18-kDa high affinity drug- and cholesterol-binding protein that is involved in various cell functions, including cell proliferation and apoptosis. PBR was shown to be overexpressed in certain types of malignant human tumors and cancer cell lines, correlating with enhanced tumorigenicity and cell proliferation rates. The present study was conducted in order to further define the role of PBR in cancer and to extend our recent findings regarding the possible anticancer effects of the standardized Ginkgo biloba extract EGb 761. Treatment with EGb 761 decreased PBR mRNA levels and inhibited the proliferation of breast, glioma and hepatocarcinoma cell lines, further corroborating our previous contention that its mechanism of action is through the modification of PBR expression. In vivo treatment with Ginkgo biloba extract led to dose-dependent decreases in xenograft growth of both MDA-MB-231 breast cancer and U-87 glioma cell lines in nude mice, although the effects were not maintained after 50 days of treatment in the latter. The results obtained in MDA-MB-231 xenografts indicated pronounced inhibition of tumor growth, verified by MRI imaging. These results were obtained using a modified experimental protocol where the animals were treated with the extract before cell inoculation. Although an exact role for PBR in relation to the initiation and progression of various types of cancer remains to be defined, our results indicate that PBR overexpression in certain cancer cells is related to an aggressive phenotype. Since EGb 761 treatment opposes this aggressive phenotype by decreasing PBR overexpression, it could be useful in preventing or treating cancer invasiveness and metastasis.
外周型苯二氮䓬受体（PBR）是一种18 kDa的高亲和力药物及胆固醇结合蛋白，参与多种细胞功能，包括细胞增殖和凋亡。研究表明，PBR在某些类型的人类恶性肿瘤和癌细胞系中过度表达，与增强的致瘤性和细胞增殖率相关。本研究旨在进一步明确PBR在癌症中的作用，并扩展我们最近关于标准化银杏叶提取物EGb 761可能的抗癌作用的研究结果。用EGb 761处理可降低PBR mRNA水平，并抑制乳腺癌、胶质瘤和肝癌细胞系的增殖，进一步证实了我们之前的观点，即其作用机制是通过改变PBR表达。在裸鼠体内用银杏叶提取物处理导致MDA-MB-231乳腺癌和U-87胶质瘤细胞系异种移植瘤生长呈剂量依赖性降低，尽管后者在治疗50天后效果未持续。在MDA-MB-231异种移植瘤中获得的结果表明肿瘤生长受到明显抑制，这通过MRI成像得到证实。这些结果是使用改良的实验方案获得的，即在细胞接种前用提取物处理动物。尽管PBR在各种类型癌症的发生和发展中的确切作用仍有待确定，但我们的结果表明，某些癌细胞中PBR的过度表达与侵袭性表型有关。由于EGb 761治疗通过降低PBR的过度表达来对抗这种侵袭性表型，它可能有助于预防或治疗癌症的侵袭和转移。
