Evidence map›Paper›PMID 26164004›Full record

ArticleTumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine2015

Metformin inhibits the proliferation, metastasis, and cancer stem-like sphere formation in osteosarcoma MG63 cells in vitro.

Xu Chen, Chuanzhen Hu, Weibin Zhang, Yuhui Shen, Jun Wang, Fangqiong Hu, Pei Yu

Abstract read
PubMed Publisher
In one paragraph

Article in Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
4.2field-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

29 citing papers in PubMed, 48 citations in OpenAlex.

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  8. [Effects of antihyperglycemics on endothelial progenitor cells].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2020
    Article
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  11. Protein PEGylation for cancer therapy: bench to bedside.Journal of cell communication and signaling · 2019
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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 2 institutions in 1 country.

Xu ChenShanghai Key Laboratory for Prevention and Treatment of Bone and joint Diseases with Integrated Chinese-Western Medicine, Shanghai Institute of Orthopedics and Traumatology, Shanghai, 20025, People's Republic of China.
Chuanzhen HuShanghai Key Laboratory for Prevention and Treatment of Bone and joint Diseases with Integrated Chinese-Western Medicine, Shanghai Institute of Orthopedics and Traumatology, Shanghai, 20025, People's Republic of China.
Weibin ZhangShanghai Key Laboratory for Prevention and Treatment of Bone and joint Diseases with Integrated Chinese-Western Medicine, Shanghai Institute of Orthopedics and Traumatology, Shanghai, 20025, People's Republic of China. weibinzhang6462@163.com.
Yuhui ShenShanghai Key Laboratory for Prevention and Treatment of Bone and joint Diseases with Integrated Chinese-Western Medicine, Shanghai Institute of Orthopedics and Traumatology, Shanghai, 20025, People's Republic of China. yuhuiss@163.com.
Jun WangShanghai Key Laboratory for Prevention and Treatment of Bone and joint Diseases with Integrated Chinese-Western Medicine, Shanghai Institute of Orthopedics and Traumatology, Shanghai, 20025, People's Republic of China.
Fangqiong HuShanghai Key Laboratory for Prevention and Treatment of Bone and joint Diseases with Integrated Chinese-Western Medicine, Shanghai Institute of Orthopedics and Traumatology, Shanghai, 20025, People's Republic of China.
Pei YuDepartment of Orthopaedics, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 20025, People's Republic of China.
Ruijin Hospital · CNIntegrated Chinese Medicine (China) · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Metformin is an oral drug that has been widely used to treat type 2 diabetes mellitus. Interestingly, accumulated evidence indicate that metformin may reduce the risk of cancer in patients with type 2 diabetes and inhibit tumor cell growth and survival in numerous malignancies, including osteosarcoma (OS) cells. In the present study, we aimed to investigate the effects of metformin on the proliferation, migration, invasion, and sphere formation in OS MG63 cells in vitro. Metformin suppressed OS MG63 cell proliferation in a dose- and time-dependent manner and markedly blocked anti-metastatic potentials, migration, and invasion, by downregulating matrix metalloproteinase 2 (MMP2) and MMP9. Besides, we established OS cancer stem-like cell (CSC) model with sarcosphere formation assay and demonstrated that metformin posed damage on CSCs in OS by inhibiting sphere formation and by inducing their stemness loss. The stemness of CSCs in OS such as self-renewal and differentiation potentials was both impaired with a significant decrease of Oct-4 and Nanog activation. Consistent with this, the positive rates of CD90, CD133, and stage-specific embryonic antigen-4 (SSEA-4) were all observed with reductions in response to metformin exposure. In addition, Western blot showed that metformin activated AMPKα at Tyr172, followed by a downregulated phosphorylation of mammalian target of rapamycin (mTOR)/S6 and feedback activation of p-AKT Ser(473) in both OS MG63 cells and CSCs. This indicates that AMPK/mTOR/S6 signaling pathway might be involved in the growth inhibition of both OS MG63 cells and CSCs. These results suggest that metformin, a potential anti-neoplastic agent, might make it a novel therapeutic choice for the treatment of OS in the future.

Indexed as

AMP-Activated Protein KinasesAnimalsApoptosisCell CycleCell Line, TumorCell MovementCell ProliferationDiabetes Mellitus, Type 2FemaleGene Expression Regulation, NeoplasticHomeodomain ProteinsHumansMatrix Metalloproteinase 2Matrix Metalloproteinase 9MetforminNanog Homeobox ProteinAMP-Activated Protein KinasesHomeodomain ProteinsMatrix Metalloproteinase 2Matrix Metalloproteinase 9MetforminMMP2 protein, humanMMP9 protein, humanNanog Homeobox ProteinNANOG protein, humanOctamer Transcription Factor-3PRKAA1 protein, humanAMPK/mTOR/S6 signaling pathwayCancer stem-like cellsMetastasisMetforminOsteosarcoma

Identifiers

PMID26164004
OpenAlexW888759873

What OpenQuestion holds

Texttitle and abstract
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.