Research question

Does recombinant pigment epithelium derived factor (PEDF) have potential in treating uterine fibroids?

Design

In-vitro models that used human leiomyoma and Eker rat uterine leiomyoma (ELT-3) cell lines. The ELT-3 cell line was used to examine cellular targets after adding recombinant PEDF to the culture media. Athymic nude female mice were used as an in-vivo model. They were injected with ELT-3 cells to induce ectopic fibroid lesions, then treated with recombinant PEDF.

Results

RNA expression of PEDF and its receptors was found in both leiomyoma cell lines, as well as the expression of PEDF receptors. Addition of recombinant PEDF to the culture medium of leiomyoma cell lines activated ERK in a time-dependent manner, induced down-regulation of vascular endothelial growth factor mRNA and protein, as well as the mRNAs of oestrogen receptors alpha and beta and inhibited cellular proliferation. Treatment of mice-bearing fibroids with recombinant PEDF reduced fibroid growth rate and resulted in smaller tumours.

Conclusions

This study suggests that recombinant PEDF is a putative novel potent physiological treatment for uterine fibroids. It targets several cornerstones of fibroid pathobiology in parallel, including vascular endothelial growth factor and oestrogen receptors, which are needed for vascularization, and restricts fibroid growth and final size in an animal model.

中文翻译：

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色素上皮衍生因子作为子宫肌瘤的新型多靶点治疗方法。

研究问题

重组色素上皮衍生因子（PEDF）在治疗子宫肌瘤方面是否具有潜力？

设计

使用人平滑肌瘤和Eker大鼠子宫平滑肌瘤（ELT-3）细胞系的体外模型。将重组PEDF加入培养基后，ELT-3细胞系用于检查细胞靶标。无胸腺裸性雌性小鼠用作体内模型。他们被注射ELT-3细胞诱导异位肌瘤病变，然后用重组PEDF处理。

结果

在平滑肌瘤细胞系和PEDF受体的表达中均发现了PEDF及其受体的RNA表达。向平滑肌瘤细胞系的培养基中添加重组PEDF以时间依赖性方式激活ERK，诱导血管内皮生长因子mRNA和蛋白以及雌激素受体α和βmRNA的下调，并抑制细胞增殖。用重组PEDF处理带有小鼠的肌瘤会降低肌瘤的生长速度并导致较小的肿瘤。

结论

这项研究表明，重组PEDF是子宫肌瘤的一种潜在的新型有效生理治疗方法。它同时靶向多种肌瘤病理生物学的基石，包括血管生成所需的血管内皮生长因子和雌激素受体，并限制了动物模型中肌瘤的生长和最终大小。