A comparison between the effects of metformin and megestrol on simple endometrial hyperplasia

Sharifzadeh, Fatemeh; Aminimoghaddam, Soheila; Kashanian, Maryam; Fazaeli, Masoomeh; Sheikhansari, Narges

doi:10.1080/09513590.2016.1223285

Cited by 16 publications

(8 citation statements)

References 17 publications

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“…As reported by another study, metformin attenuates estrogen and tamoxifen induced EH by inhibiting S6K1 activation by mTOR [ 114 ]. Data derived from in vivo studies as well as clinical trials show that metformin is comparable to progestins for the treatment of simple endometrial hyperplasia [ 115 , 116 ]. The fact that metformin acts in the endometrium via downregulating the mTOR pathway highlights the importance of this signaling cascade in EH.…”

Section: Mtor and Eif Signaling In Benign Endometrial Diseasesmentioning

confidence: 99%

The Role of mTOR and eIF Signaling in Benign Endometrial Diseases

Driva

Schatz

Sobočan

et al. 2022

IJMS

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Adenomyosis, endometriosis, endometritis, and typical endometrial hyperplasia are common non-cancerous diseases of the endometrium that afflict many women with life-impacting consequences. The mammalian target of the rapamycin (mTOR) pathway interacts with estrogen signaling and is known to be dysregulated in endometrial cancer. Based on this knowledge, we attempt to investigate the role of mTOR signaling in benign endometrial diseases while focusing on how the interplay between mTOR and eukaryotic translation initiation factors (eIFs) affects their development. In fact, mTOR overactivity is apparent in adenomyosis, endometriosis, and typical endometrial hyperplasia, where it promotes endometrial cell proliferation and invasiveness. Recent data show aberrant expression of various components of the mTOR pathway in both eutopic and ectopic endometrium of patients with adenomyosis or endometriosis and in hyperplastic endometrium as well. Moreover, studies on endometritis show that derangement of mTOR signaling is linked to the establishment of endometrial dysfunction caused by chronic inflammation. This review shows that inhibition of the mTOR pathway has a promising therapeutic effect in benign endometrial conditions, concluding that mTOR signaling dysregulation plays a critical part in their pathogenesis.

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Section: Mtor and Eif Signaling In Benign Endometrial Diseasesmentioning

confidence: 99%

The Role of mTOR and eIF Signaling in Benign Endometrial Diseases

Driva

Schatz

Sobočan

et al. 2022

IJMS

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show abstract

“…A previous clinical trial revealed that the effect of Met is comparable with that of megestrol for the treatment of simple EH (23). Another study demonstrated that Met may directly reverse impaired glycolysis and normalize mitochondrial function in PcOS patients with EH (24).…”

Section: Discussionmentioning

confidence: 99%

Metformin alleviates endometrial hyperplasia through the UCA1/miR‑144/TGF‑β1/AKT signaling pathway

Guo¹,

Zhou²,

Huang

2019

Int J Mol Med

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The objective of the present study was to investigate the molecular mechanism underlying the role of metformin (Met) in reducing the risk of endometrial hyperplasia (EH). Reverse transcription-quantitative polymerase chain reaction, western blot and immunohistochemistry (IHc) assays were used to study the effects of Met and tamoxifen on the expression levels of urothelial cancer associated 1 (UcA1), microRNA-144 (miR-144) and other factors along the transforming growth factor-β1 (TGF-β1)/protein kinase B (AKT) signaling pathway. In addition, MTT and flow cytometry assays were performed to detect the effect of Met on cell proliferation and apoptosis. Tamoxifen treatment increased the weight of the uterus and the level of UcA1, while decreasing the expression of miR-144. In addition, treatment with tamoxifen (2.0 and 3.5 µg) upregulated the protein expression levels of TGF-β and p-AKT, while downregulating the protein expression of active caspase-3 in a dose-dependent manner. By contrast, Met reduced cell viability, promoted cell apoptosis, and reduced the expression levels of UcA1, TGF-β and p-AKT, while upregulating the expression of miR-144 and active caspase-3 in a dose-dependent manner. Furthermore, Met also reduced the weight of uterus. However, tamoxifen and Met did not exert any effect on the protein levels of total AKT and total caspase-3. The levels of TGF-β and p-AKT proteins in the EH group were much higher when compared with those in the sham group, while Met treatment reduced these protein levels to a certain extent. In addition, the expression of active caspase-3 in the EH group was much lower than that in the sham group, while Met treatment increased its level to a certain extent. In conclusion, the current study suggested that Met reduces the risk of EH by reducing the expression levels of UcA1, TGF-β and p-AKT, while increasing the levels of miR-144 and active caspase-3 in a dose-dependent manner.

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“…29,30 The clinical safety and efficacy of megestrol application have been identified in multiple randomized, double-blind and placebocontrolled trials. [31][32][33] However, the exact anticancer molecular mechanism involved is not completely known.…”

Section: Discussionmentioning

confidence: 99%

“…15,34 Despite inhibiting the secretion of progesterone in pituitary gland, it is supposed that other potential mechanisms are also implicated in its anticancer roles. 31 In this study, we investigated the role of megestrol acetate in regulating survival and growth of endometrial cancer cells. Megestrol acetate treatment reduced the proliferation of Ishikawa cells and HHUA cells in vitro, suggesting that megestrol acetate is an anticancer agent in endometrial cancer by directly influencing tumor cell growth.…”

Section: Discussionmentioning

confidence: 99%

Megestrol acetate drives endometrial carcinoma cell senescence via interacting with progesterone receptor B/FOXO1 axis

Wang

Shi

2021

Exp Biol Med (Maywood)

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Megestrol acetate is a common and efficient anticancer progesterone. To explore the activity and the therapeutic mechanisms of megestrol acetate in endometrial cancer, human endometrial cancer cell lines Ishikawa and HHUA overexpressing progesterone receptor A (PR-A) and progesterone receptor B (PR-B) were treated with megestrol acetate. Cell viability, apoptosis, cycle arrest, and senescence, as well as the expressions of p21 and p16, two hallmarks of cellular senescence, were evaluated. Compared with the control, >10 nmol/L megestrol acetate treatment could significantly reduce endometrial cancer cell growth, and induce the irreversible G1 arrest and cell senescence. The expression of cyclin D1 in megestrol acetate treated cells was downregulated, while the expressions of p21 and p16 were upregulated via PR-B isoform. FOXO1 inhibitor AS1842856 could significantly abrogate megestrol acetate-induced cell senescence, suggesting that FOXO1 was involved in megestrol acetate/PR-B axis. These findings may provide a new understanding for the treatment of human endometrial cancer.

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A comparison between the effects of metformin and megestrol on simple endometrial hyperplasia

Abstract: Metformin is comparable with megestrol for the treatment of simple endometrial hyperplasia.

Cited by 16 publications

References 17 publications

The Role of mTOR and eIF Signaling in Benign Endometrial Diseases

The Role of mTOR and eIF Signaling in Benign Endometrial Diseases

Metformin alleviates endometrial hyperplasia through the UCA1/miR‑144/TGF‑β1/AKT signaling pathway

Megestrol acetate drives endometrial carcinoma cell senescence via interacting with progesterone receptor B/FOXO1 axis

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