Medroxyprogesterone Reverses Tolerable Dose Metformin-Induced Inhibition of Invasion via Matrix Metallopeptidase-9 and Transforming Growth Factor-β1 in KLE Endometrial Cancer Cells

Suh, Dong Hoon; Lee, Sunray; Park, Hyun Sook; Park, Noh Hyun

doi:10.3390/jcm9113585

Cited by 5 publications

(3 citation statements)

References 33 publications

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“…1 ) ( Xiao et al ., 2012 ). Furthermore, metformin showed growth inhibition in HEC-1-A cells ( Zhang et al ., 2017 ) and invasion inhibitory effects in KLE cells ( Suh et al ., 2020 ), the growth inhibition effect of metformin in these cell lines was not observed in our data ( Fig. 1 ).…”

Section: Discussionmentioning

confidence: 99%

Knockdown of LKB1 Sensitizes Endometrial Cancer Cells via AMPK Activation

Rho

Byun

Kim

et al. 2021

Biomol Ther (Seoul)

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Metformin is an anti-diabetic drug and has anticancer effects on various cancers. Several studies have suggested that metformin reduces cell proliferation and stimulates cell-cycle arrest and apoptosis. However, the definitive molecular mechanism of metformin in the pathophysiological signaling in endometrial tumorigenesis and metastasis is not clearly understood. In this study, we examined the effects of metformin on the cell viability and apoptosis of human cervical HeLa and endometrial HEC-1-A and KLE cancer cells. Metformin suppressed cell growth in a dose-dependent manner and dramatically evoked apoptosis in HeLa cervical cancer cells, while apoptotic cell death and growth inhibition were not observed in endometrial (HEC-1-A, KLE) cell lines. Accordingly, the p27 and p21 promoter activities were enhanced while Bcl-2 and IL-6 activities were significantly reduced by metformin treatment. Metformin diminished the phosphorylation of mTOR, p70S6K and 4E-BP1 by accelerating adenosine monophosphateactivated kinase (AMPK) in HeLa cancer cells, but it did not affect other cell lines. To determine why the anti-proliferative effects are observed only in HeLa cells, we examined the expression level of liver kinase B1 (LKB1) since metformin and LKB1 share the same signalling system, and we found that the LKB1 gene is not expressed only in HeLa cancer cells. Consistently, the overexpression of LKB1 in HeLa cancer cells prevented metformin-triggered apoptosis while LKB1 knockdown significantly increased apoptosis in HEC-1-A and KLE cancer cells. Taken together, these findings indicate an underlying biological/physiological molecular function specifically for metformin-triggered apoptosis dependent on the presence of the LKB1 gene in tumorigenesis.

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Section: Discussionmentioning

confidence: 99%

Knockdown of LKB1 Sensitizes Endometrial Cancer Cells via AMPK Activation

Rho

Byun

Kim

et al. 2021

Biomol Ther (Seoul)

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“…Each sample was divided into six portions (100 μl each, some samples had less than six due to the limit volume of blood) and were added to the 48-well plate (Supplementary Fig 5-A). Six replicates of each person were added different reagents at reported concentrations (100 μ M Aspirin 46 (Selleck, S3017), 50 μ g/ml Curcumin 47 (Selleck, S1039), 50 μ M Resveratrol 48 (Selleck, S1396), 500 μ M NMN 49 (Qingyuan Shengyi Biological Technology Co., Ltd.), 100 μ M Metformin 50 (Selleck, S1950), 100ng/ml LPS(Sigma, L2880) respectively. Then these samples were incubated and constantly rotated on a shaker at 6 rpm, 37°C for 24 hours 51 .…”

Section: Methodsmentioning

confidence: 99%

Scale Bar of Aging Trajectories for Screening Personal Rejuvenation Treatments

Shen

Jiang

et al. 2022

Preprint

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Although aging is an increasingly severe healthy, economic, and social global problem, it is far from well-modeling aging due to the aging process's complexity. To promote the aging modeling, here we did the quantitative measurement based on aging blood transcriptome. Specifically, the aging blood transcriptome landscape was constructed through ensemble modeling in a cohort of 505 people, and 1138 age-related genes were identified. To assess the aging rate in the linear dimension of aging, we constructed a simplified linear aging clock, which distinguished fast-aging and slow-aging populations and showed the differences in the composition of immune cells. Meanwhile, the non-linear dimension of aging revealed the transcriptome fluctuations with a crest around the age of 40 and showed that this crest came earlier and was more vigorous in the fast-aging population. Moreover, the aging clock was applied to evaluate the rejuvenation effect of molecules in vitro, such as Nicotinamide Mononucleotide (NMN) and Metformin. In sum, this study developed a de novo aging clock to evaluate age-dependent precise medicine by revealing its fluctuation nature based on comprehensively mining the aging blood transcriptome, promoting the development of personal aging monitoring and anti-aging therapies.

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“…Metformin on the other hand seems to regulate central carbon metabolism which in turn regulates mitochondrial activity and nucleotide production that are essential for the development and sustain of tumors [32,33]. Its ability to negatively affect cell invasion through modulation of the levels of matrix metalloproteinases and other enzymes has been also reported in preclinical studies [34]. Another potential pathway linking metformin with the aims of fertility sparing surgery is the fact that progestin treatment induces prolactin secretion which in turn stimulates cell proliferation and induces endometrial decidualization, thus, in some cases diminishing the effect that is expected [35].…”

Section: Treatment and Follow-up Optionsmentioning

confidence: 98%

New boundaries for fertility sparing management in endometrial cancer

Rodolakis¹,

Pergialiotis²,

Thomakos³

2023

Current Opinion in Oncology

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Purpose of review The increasing rates of endometrial cancer in premenopausal women that accompanies modern lifestyle options that enhance the prevalence of obesity as well as the trend of delayed childbearing are expected to increase the need for fertility sparing techniques. Currently, the cornerstone of fertility sparing treatment is hormonal handling with progestin treatment and is reserved for women with well differentiated endometrioid lesions that are limited in the myometrial layer. Recent findings Innovative approaches in the surgical treatment of patients with the use of operative hysteroscopy seem to offer decreased intervals to remission of lesions and longer progression free survival. Recent small case series also dictate that patients with endometrioid lesions of medium differentiation as well as those with superficial myometrial invasion may be adequately treated with the use of operative hysteroscopy. Moreover, the novel classification system may help better understand patients that will likely respond better to hormonal treatment. Summary In the near future, further data from clinical trials will be available that will help optimize patient selection as well select surgical and medical options that will help establish a personalized approach of fertility preservation in endometrial cancer patients.

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Medroxyprogesterone Reverses Tolerable Dose Metformin-Induced Inhibition of Invasion via Matrix Metallopeptidase-9 and Transforming Growth Factor-β1 in KLE Endometrial Cancer Cells

Cited by 5 publications

References 33 publications

Knockdown of LKB1 Sensitizes Endometrial Cancer Cells via AMPK Activation

Knockdown of LKB1 Sensitizes Endometrial Cancer Cells via AMPK Activation

Scale Bar of Aging Trajectories for Screening Personal Rejuvenation Treatments

New boundaries for fertility sparing management in endometrial cancer

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