Evidence map›Paper›PMID 26544558›Full record

ArticlePloS one2015

Synergistic Effect and Molecular Mechanism of Homoharringtonine and Bortezomib on SKM-1 Cell Apoptosis.

Jing Zhang, Bobin Chen, Ting Wu, Qian Wang, Lin Zhuang, Chen Zhu, Ni Fan, Wenjiao Qing, Yan Ma, Xiaoping Xu

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

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.1field-weighted citation impact, top 21% 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

5 citing papers in PubMed, 9 citations in OpenAlex.

  1. Article
  2. Review
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  5. Cephalotaxus Alkaloids.The Alkaloids. Chemistry and biology
    Review
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

10 authors at 2 institutions in 1 country.

Jing ZhangDepartment of Hematology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
Bobin ChenDepartment of Hematology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
Ting WuDepartment of Hematology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
Qian WangDepartment of Hematology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
Lin ZhuangDepartment of Hematology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
Chen ZhuDepartment of Hematology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
Ni FanDepartment of Hematology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
Wenjiao QingDepartment of Hematology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
Yan MaDepartment of Hematology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
Xiaoping XuDepartment of Hematology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
Fudan University · CNHuashan Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMyelodysplastic syndromes (MDS) are clonal marrow stem-cell disorders with a high risk of progression to acute myeloid leukemia (AML). Treatment options are limited and targeted therapies are not available for MDS. In the present study, we investigated the cytotoxicity and the molecular mechanism of Homoharringtonine (HHT) and Bortezomib towards high-risk MDS cell line SKM-1 in vitro and the role of miR-3151 was first evaluated in SKM-1 cells.

methodsSKM-1 cells were treated with different concentrations of HHT or Bortezomib, and cell viability was analyzed with CCK-8 assay. The influence on cell proliferation, cell cycle distribution and the percentage of apoptosis cells were analyzed by flow cytometry. Calcusyn software was used to calculate combination index (CI) values. Western blot was used to analysis phosphorylation of Akt and nuclear NF-κB protein expression in SKM-1 cells. Mature miR-3151 level and p53 protein level were detected after HHT or Bortezomib treatment. The cell proliferation and p53 protein level were reassessed in SKM-1 cells infected with lentivirus to overexpress miR-3151.

resultsSimultaneous exposure to HHT and Bortezomib (10.4:1) resulted in a significant reduction of cell proliferation in SKM-1 cells (P < 0.05). Cell cycle arrest at G0/G1 and G2/M phase was observed (P < 0.05). HHT and Bortezomib synergistically induced cell apoptosis by regulating members of caspase 9, caspase 3 and Bcl-2 family (P < 0.01). The mechanisms of the synergy involved Akt and NF-κB signaling pathway inhibition, downregulation of mature miR-3151 and increment of downstream p53 protein level. Overexpression of miR-3151 promoted cell proliferation and inhibited p53 protein expression in SKM-1 (P < 0.01).

conclusionsHHT and Bortezomib synergistically inhibit SKM-1 cell proliferation and induce apoptosis in vitro. Inhibition of Akt and NF-κB pathway signaling contribute to molecular mechanism of HHT and Bortezomib. miR-3151 abundance is implicated in SKM-1 cell viability, cell proliferation and p53 protein expression.

Indexed as

ApoptosisBortezomibCell CycleCell LineCell ProliferationCell SurvivalFlow CytometryHarringtoninesHomoharringtonineHumansNF-kappa BSignal TransductionSoftwareBortezomibHarringtoninesHomoharringtonineNF-kappa B

Identifiers

PMID26544558
PMCPMC4636319
OpenAlexW2255213519

What OpenQuestion holds

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LicenceCC BY
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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.