Evidence map›Paper›PMID 26718286›Full record

ArticleStem cell research & therapy2015

Inhibitory effects of metformin at low concentration on epithelial-mesenchymal transition of CD44(+)CD117(+) ovarian cancer stem cells.

Rongrong Zhang, Ping Zhang, Hong Wang, Dongming Hou, Wentao Li, Guishan Xiao, Chenwei Li

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Stem cell research & therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.

0numbers the graph read from it
0cells of the map it votes in
52citing papers in PubMed
4.4field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

52 citing papers in PubMed, 95 citations in OpenAlex.

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  12. Targeting ovarian cancer stem cells: a new way out.Stem cell research & therapy · 2023
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 5 institutions in 1 country.

Rongrong ZhangDepartment of Gynecology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200092, China. rrzhangcn@126.com.
Ping ZhangDepartment of Gynecology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200092, China. pingzhang_xhyy@126.com.
Hong WangDepartment of Gynecology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200092, China. hongwang_xhyy@163.com.
Dongming HouDepartment of Otolaryngology & Head and Neck Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200092, China. hdm1968@hotmail.com.
Wentao LiDepartment of Interventional Radiology, Cancer Hospital, Fudan University, Shanghai, 200032, China. liwentao98@126.com.
Guishan XiaoSchool of Pharmaceutical Science and Technology, Dalian University of Technology, Dalian, 116024, China. gxiao@dlut.edu.cn.
Chenwei LiSunstem Biotechnology Co., Ltd, Shanghai, 200439, China. sunstem1@163.com.
Shanghai Jiao Tong University · CNXinHua Hospital · CNDalian University of Technology · CNFudan University Shanghai Cancer Center · CNShanghai CASB Biotechnology (China) · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAlthough metformin, a first-line drug for treating diabetes, may play an important role in inhibition of epithelial ovarian cancer cell growth and cancer stem cells (CSCs), metformin at low dose showed less effect on the proliferation of ovarian cancer cells. In this study, we evaluated the effect of metformin at low dose on ovarian CSCs in order to understand the molecular mechanisms underlying.

methodsThe inhibitory effects of metformin at los dose on proliferation and population of ovarian cancer cells including SKOV3 and A2780 were assessed by cell proliferation assay and flow cytometry. Quantitative real-time PCR assay on expression of Bcl-2, Survivin and Bax was performed to determine the effect of metformin at low dose on epithelial-mesenchymal transition (EMT) of cancer cells and CSCs. Tumor sphere formation assay was also performed to evaluate the effect of metformin on spheres forming ability of CSCs. The therapeutic efficacy and the anti-CSC effects of metformin at low dose were investigated by using both SKOV3 cells and primary tumor xenografts. In addition, the CSC frequency and EMT in tumor xenograft models were also assessed by flow cytometry and quantitative real-time PCR.

resultsMetformin at low dose did not affect the proliferation of ovarian cancer cells. However, it inhibited population of CD44(+)CD117(+) selectively, neither CD133(+) nor ALDH(+) cells. It suppressed expression of snail2, twist and vimentin significantly in cancer cells and CD44(+)CD117(+) CSCs in vitro. Low dose of metformin reduced survivin expression in CSCs. Low concentrations of metformin inhibited the secondary and the tertiary tumor sphere formation, decreased SKOV3 and primary ovarian tumor xenograft growth, enhanced the anticancer effect of cisplatin, and lowered the proportion of CD44(+)CD117(+) CSCs in the xenograft tissue. Metformin was also associated with a reduction of snail2, twist, and vimentin in CD44(+)CD117(+) ovarian CSCs in vivo.

conclusionsOur results implicate that metformin at low dose inhibits selectively CD44(+)CD117(+) ovarian CSCs through inhibition of EMT and potentiates the effect of cisplatin.

Indexed as

AnimalsAntineoplastic Agentsbcl-2-Associated X ProteinCell Line, TumorCell ProliferationCisplatinEpithelial-Mesenchymal TransitionFemaleHumansHyaluronan ReceptorsInhibitor of Apoptosis ProteinsMaleMetforminMiceMice, Inbred NODMice, NudeAntineoplastic Agentsbcl-2-Associated X ProteinBIRC5 protein, humanCisplatinHyaluronan ReceptorsInhibitor of Apoptosis ProteinsMetforminProto-Oncogene Proteins c-bcl-2Proto-Oncogene Proteins c-kitSNAI1 protein, humanSnai1 protein, mouseSnail Family Transcription FactorsSurvivinTranscription FactorsVimentin

Identifiers

PMID26718286
PMCPMC4697317
OpenAlexW2208454568

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.