脂质体增强磷铂的抗肿瘤作用部分是通过上调乳腺癌中色素上皮衍生因子（PEDF）实现的。

Phosphaplatin Anti-tumor Effect Enhanced by Liposomes Partly an Up-regulation of PEDF in Breast Cancer.

作者信息

Belkacemi Louiza, Atkins Jason L, Yang L U, Gadgil Prajakta, Sater Amy K, Chow Diana S, Bose Rathindra N, Zhang Shaun Xiaoliu

机构信息

Department of Biology and Biochemistry, University of Houston, Houston, TX, U.S.A.

Center for Nuclear Receptors and Cell Signaling, University of Houston, Houston, TX, U.S.A.

出版信息

Anticancer Res. 2018 Feb;38(2):623-646. doi: 10.21873/anticanres.12267.

DOI:10.21873/anticanres.12267

PMID:29374685

Abstract

BACKGROUND/AIM: Phosphaplatin platinum (IV) (RRD4) complex has exceptional antitumor properties. The aim of this study was to investigate the effects and the mechanism of action of free and liposome-encapsulated RRD4 in breast cancer.

MATERIALS AND METHODS

Liposome-encapsulated RRD4 prepared by thin-film dehydration: hydration and free RRD4 were tested in vivo and in vitro against 4T1 breast cancer cells. Cell proliferation, migration and viability were determined. Tissue and cell production and expression of pigment epithelium-derived factor (PEDF) were assessed by ELISA and western blot. 4T1 cells treated with PEDF siRNA were evaluated for viability and apoptosis.

RESULTS

RRD4 inhibited tumor growth and prevented distant metastasis. Liposome formulation enhanced this therapeutic benefit without increasing toxicity and prolonged RRD4 retention in tumor tissues. In vitro, RRD4 induced 4T1 apoptosis through up-regulation of FAS, BAX, and PUMA, and down-regulation of BCL2. RRD4 facilitates a FAS-intrinsic signaling mechanism. PEDF up-regulation represents another antitumor mechanism associated with this phosphaplatin compound.

DISCUSSION

Free RRD4 or formulated into liposomes, are excellent candidates for adjuvant therapy against breast tumor growth and metastasis.

摘要

背景/目的：磷酸铂（IV）（RRD4）复合物具有卓越的抗肿瘤特性。本研究旨在探究游离型和脂质体包裹型RRD4对乳腺癌的作用及其作用机制。

材料与方法

采用薄膜脱水法制备脂质体包裹型RRD4：对水化型和游离型RRD4进行体内和体外抗4T1乳腺癌细胞试验。测定细胞增殖、迁移和活力。通过酶联免疫吸附测定法（ELISA）和蛋白质免疫印迹法评估组织和细胞中色素上皮衍生因子（PEDF）的产生和表达。对用PEDF小干扰RNA（siRNA）处理的4T1细胞的活力和凋亡情况进行评估。

结果

RRD4抑制肿瘤生长并预防远处转移。脂质体制剂增强了这种治疗效果，且不增加毒性，并延长了RRD4在肿瘤组织中的滞留时间。在体外，RRD4通过上调FAS、BAX和PUMA以及下调BCL2诱导4T1细胞凋亡。RRD4促进一种FAS内在信号传导机制。PEDF上调是与这种磷酸铂化合物相关的另一种抗肿瘤机制。