Evidence map›Paper›PMID 28865485›Full record

ArticleJournal of experimental & clinical cancer research : CR2017

Combination therapy of PKCζ and COX-2 inhibitors synergistically suppress melanoma metastasis.

Ping Zhou, Jiaqi Qin, Yuan Li, Guoxia Li, Yinsong Wang, Ning Zhang, Peng Chen, Chunyu Li

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Journal of experimental & clinical cancer research : CR, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
4.6field-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

26 citing papers in PubMed, 56 citations in OpenAlex.

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  20. The Role of Cyclooxygenase-2 in Colorectal Cancer.International journal of medical sciences · 2020
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Ping ZhouDepartment of Thoracic Medical Oncology, Tianjin Medical University Cancer Institute and Hospital, School of Basic Medical Sciences, International Medical School, School of Pharmacy, Tianjin Medical University, No. 22 Qixiangtai Road, Heping District, Tianjin, 300070, People's Republic of China.
Jiaqi QinDepartment of Thoracic Medical Oncology, Tianjin Medical University Cancer Institute and Hospital, School of Basic Medical Sciences, International Medical School, School of Pharmacy, Tianjin Medical University, No. 22 Qixiangtai Road, Heping District, Tianjin, 300070, People's Republic of China.
Yuan LiDepartment of Thoracic Medical Oncology, Tianjin Medical University Cancer Institute and Hospital, School of Basic Medical Sciences, International Medical School, School of Pharmacy, Tianjin Medical University, No. 22 Qixiangtai Road, Heping District, Tianjin, 300070, People's Republic of China.
Guoxia LiDepartment of Thoracic Medical Oncology, Tianjin Medical University Cancer Institute and Hospital, School of Basic Medical Sciences, International Medical School, School of Pharmacy, Tianjin Medical University, No. 22 Qixiangtai Road, Heping District, Tianjin, 300070, People's Republic of China.
Yinsong WangDepartment of Thoracic Medical Oncology, Tianjin Medical University Cancer Institute and Hospital, School of Basic Medical Sciences, International Medical School, School of Pharmacy, Tianjin Medical University, No. 22 Qixiangtai Road, Heping District, Tianjin, 300070, People's Republic of China.
Ning ZhangDepartment of Thoracic Medical Oncology, Tianjin Medical University Cancer Institute and Hospital, School of Basic Medical Sciences, International Medical School, School of Pharmacy, Tianjin Medical University, No. 22 Qixiangtai Road, Heping District, Tianjin, 300070, People's Republic of China.
Peng ChenDepartment of Thoracic Medical Oncology, Tianjin Medical University Cancer Institute and Hospital, School of Basic Medical Sciences, International Medical School, School of Pharmacy, Tianjin Medical University, No. 22 Qixiangtai Road, Heping District, Tianjin, 300070, People's Republic of China. chenpengdoc@sina.com.
Chunyu LiDepartment of Thoracic Medical Oncology, Tianjin Medical University Cancer Institute and Hospital, School of Basic Medical Sciences, International Medical School, School of Pharmacy, Tianjin Medical University, No. 22 Qixiangtai Road, Heping District, Tianjin, 300070, People's Republic of China. lichunyu@tmu.edu.cn.
Tianjin Medical University Cancer Institute and Hospital · CNTianjin Medical University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMetastatic malignant melanoma is one of the most aggressive malignancies and its treatment remains challenging. Recent studies demonstrate that the melanoma metastasis has correlations with the heightened activations of protein kinase C ζ (PKCζ) and cyclooxygenase-2 (COX-2) signaling pathways. Targeted inhibitions for PKCζ and COX-2 have been considered as the promising strategies for the treatment of melanoma metastasis. Thus, the PKCζ inhibitor J-4 and COX-2 inhibitor Celecoxib were combined to treat melanoma metastasis in this study.

methodsThe Transwell assay, Wound-healing assay and Adhesion assay were used to evaluate the inhibition of combined therapy of J-4 and Celecoxib on melanoma cells invasion, migration and adhesion in vitro, respectively. The impaired actin polymerization was observed by confocal microscope and inactivated signal pathways about PKCζ and COX-2 were confirmed by the Western blotting assay. The B16-F10/C57BL mouse melanoma model was used to test the inhibition of combined therapy of J-4 and Celecoxib on melanoma metastasis in vivo.

resultsThe in vitro results showed that the combination of J-4 and Celecoxib exerted synergistic inhibitory effects on the migration, invasion and adhesion of melanoma B16-F10 and A375 cells with combination index less than 1. The actin polymerization and phosphorylation of Cofilin required in cell migration were severely impaired, which is due to the inactivation of PKCζ related signal pathways and the decrease of COX-2. The combined inhibition of PKCζ and COX-2 induced Mesenchymal-Epithelial Transition (MET) in melanoma cells with the expression of E-Cadherin increasing and Vimentin decreasing. The secretion of MMP-2/MMP-9 also significantly decreased after the combination treatment. In C57BL/6 mice intravenously injected with B16-F10 cells (5 × 10

conclusionsThis study demonstrates that the combination therapy of PKCζ and COX-2 inhibitors can significantly inhibit melanoma metastasis in vitro and in vivo, which will be an efficient strategy for treatment of melanoma metastasis in clinics.

Indexed as

AmidinesAnimalsBenzene DerivativesCdh1 ProteinsCelecoxibCyclooxygenase 2Cyclooxygenase 2 InhibitorsEpithelial-Mesenchymal TransitionGene Expression Regulation, NeoplasticHumansMatrix Metalloproteinase 2Matrix Metalloproteinase 9Melanoma, ExperimentalMiceNeoplasm MetastasisProtein Kinase CAmidinesBenzene DerivativesCdh1 ProteinsCelecoxibCyclooxygenase 2Cyclooxygenase 2 InhibitorsFzr1 protein, mouseJ-4 compoundMatrix Metalloproteinase 2Matrix Metalloproteinase 9Protein Kinase CProtein Kinase C zetaPtgs2 protein, mouseCelecoxibCombination therapyCox-2Melanoma metastasisPKCζ inhibitor

Identifiers

PMID28865485
PMCPMC5581453
OpenAlexW2752276546

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.