Autophagy up-regulation by ulipristal acetate as a novel target mechanism in the treatment of uterine leiomyoma: an in vitro study

醋酸乌利司他上调自噬作为子宫平滑肌瘤治疗的新靶点机制:一项体外研究

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作者:Barbara Del Bello, Paola Marcolongo, Pasquapina Ciarmela, Flavia Sorbi, Felice Petraglia, Stefano Luisi, Emilia Maellaro

Objective

To assess the effect of ulipristal acetate (UPA) on the autophagic process of uterine leiomyoma cells. Design: In vitro study in primary cultures of leiomyoma and myometrial cells isolated from biopsy specimen, and gene expression evaluation in biopsy material. Setting: Cellular pathology laboratory. Patient(s): Premenopausal women (without hormonal treatment) undergoing myomectomy or hysterectomy for symptomatic leiomyomas. Intervention(s): Surgical specimens collected from uterine leiomyomas and matched normal myometria. Main outcome measure(s): After treatment of myometrial and leiomyoma cells with UPA, autophagy was evaluated by Western blot analysis of the typical biochemical markers, LC3-II, LC3-II:LC3-I ratio, and p62/SQSTM1. The expression level of Atg7 and Atg4D proteins was also assessed by Western blot. Result(s): The increase of LC3-II protein, LC3-II:LC3-I ratio, and p62/SQSTM1 protein indicates that UPA treatment up-regulates the autophagic response in leiomyoma cells, whereas these markers were almost unchanged in myometrial cells. Consistently, an increased level of Atg7 and Atg4D proteins was observed only in UPA-treated leiomyoma cells. The autophagic machinery is put into motion selectively in these cells, despite that the basal messenger RNA levels of LC3, SQSTM1, and ATG7 in leiomyoma biopsy specimen were not significantly different from those found in normal myometrial biopsy material.

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