| Title |
Metformin inhibits the proliferation, metastasis, and cancer stem-like sphere formation in osteosarcoma MG63 cells in vitro
|
|---|---|
| Published in |
Tumor Biology, July 2015
|
| DOI | 10.1007/s13277-015-3751-1 |
| Pubmed ID | |
| Authors |
Xu Chen, Chuanzhen Hu, Weibin Zhang, Yuhui Shen, Jun Wang, Fangqiong Hu, Pei Yu |
| 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. |
X Demographics
The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Ireland | 1 | 50% |
| United Kingdom | 1 | 50% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 50% |
| Scientists | 1 | 50% |
Mendeley readers
The data shown below were compiled from readership statistics for 37 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Luxembourg | 1 | 3% |
| Unknown | 36 | 97% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 6 | 16% |
| Student > Bachelor | 6 | 16% |
| Student > Master | 4 | 11% |
| Other | 3 | 8% |
| Researcher | 3 | 8% |
| Other | 6 | 16% |
| Unknown | 9 | 24% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 14 | 38% |
| Biochemistry, Genetics and Molecular Biology | 5 | 14% |
| Pharmacology, Toxicology and Pharmaceutical Science | 2 | 5% |
| Agricultural and Biological Sciences | 2 | 5% |
| Immunology and Microbiology | 1 | 3% |
| Other | 3 | 8% |
| Unknown | 10 | 27% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 19 August 2015.
All research outputs
#15,344,095
of 22,824,164 outputs
Outputs from Tumor Biology
#1,050
of 2,622 outputs
Outputs of similar age
#153,771
of 262,571 outputs
Outputs of similar age from Tumor Biology
#49
of 176 outputs
Altmetric has tracked 22,824,164 research outputs across all sources so far. This one is in the 22nd percentile – i.e., 22% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,622 research outputs from this source. They receive a mean Attention Score of 2.2. This one has gotten more attention than average, scoring higher than 53% of its peers.
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We're also able to compare this research output to 176 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 64% of its contemporaries.