Evidence map›Paper›PMID 30288546›Full record

ArticleJournal of molecular medicine (Berlin, Germany)2018

Trichostatin A, a histone deacetylase inhibitor, induces synergistic cytotoxicity with chemotherapy via suppression of Raf/MEK/ERK pathway in urothelial carcinoma.

Wei-Chou Lin, Fu-Shun Hsu, Kuan-Lin Kuo, Shing-Hwa Liu, Chia-Tung Shun, Chung-Sheng Shi, Hong-Chiang Chang, Yu-Chieh Tsai, Ming-Chieh Lin, June-Tai Wu and 6 more

Erratum issuedAbstract read
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In one paragraph

Article in Journal of molecular medicine (Berlin, Germany), 2018. 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 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.5field-weighted citation impact, top 36% 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

7 citing papers in PubMed, 9 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 5 institutions in 1 country.

Wei-Chou LinDepartment of Pathology, College of Medicine, National Taiwan University, National Taiwan University Hospital, Taipei, Taiwan.
Fu-Shun HsuGraduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
Kuan-Lin KuoGraduate Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Shing-Hwa LiuGraduate Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Chia-Tung ShunDepartment of Pathology, College of Medicine, National Taiwan University, National Taiwan University Hospital, Taipei, Taiwan.
Chung-Sheng ShiGraduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Hong-Chiang ChangDepartment of Urology, College of Medicine, National Taiwan University, National Taiwan University Hospital, Taipei, Taiwan.
Yu-Chieh TsaiDepartment of Oncology, College of Medicine, National Taiwan University, National Taiwan University Hospital, Taipei, Taiwan.
Ming-Chieh LinGraduate Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
June-Tai WuGraduate Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
Yu KuoGraduate Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
Po-Ming ChowDepartment of Urology, College of Medicine, National Taiwan University, National Taiwan University Hospital, Taipei, Taiwan.
Shih-Ming LiaoDepartment of Urology, College of Medicine, National Taiwan University, National Taiwan University Hospital, Taipei, Taiwan.
Shao-Ping YangDepartment of Urology, College of Medicine, National Taiwan University, National Taiwan University Hospital, Taipei, Taiwan.
Jo-Yu HongDepartment of Urology, College of Medicine, National Taiwan University, National Taiwan University Hospital, Taipei, Taiwan.
Kuo-How HuangDepartment of Urology, College of Medicine, National Taiwan University, National Taiwan University Hospital, Taipei, Taiwan. khhuang123@ntu.edu.tw.
National Taiwan University Hospital · TWNational Taiwan University · TWChang Gung University · TWTaipei City Hospital · TWTaipei Veterans General Hospital · TW

Funding

Ministry of Science and Technology, Taiwan 103-2314-B-002-161-MY3Ministry of Science and Technology, Taiwan 104-2314-B-002-164-MY3National Taiwan University Hospital 103-S2349National Taiwan University Hospital 104-M2868National Taiwan University Hospital 105-28National Taiwan University Hospital 105-S2978
6 · The paper itself

Abstract

In this study, we aimed to investigate the antitumor effects of trichostatin A (TSA), an antifungal antibiotic that inhibits histone deacetylase (HDAC) family of enzymes, alone or in combination with anyone of the three chemotherapeutic agents (cisplatin, gemcitabine, and doxorubicin) for the treatment of human urothelial carcinoma (UC). Two high-grade human UC cell lines (T24 and NTUB1) were used. Cytotoxicity and apoptosis were assessed by MTT assay and flow cytometry, respectively. The expression of phospho-c-Raf, phospho-MEK1/2, and phospho-ERK1/2 was measured by western blotting. ERK siRNA knockdown and the specific MEK inhibitor U0126 were used to examine the role of Raf/MEK/ERK signaling pathway in combined cytotoxicity of TSA and chemotherapy. TSA co-treatment with any one of the three chemotherapeutic agents induced synergistic cytotoxicity (combination index < 1) and concomitantly suppressed chemotherapeutic drug-induced activation of Raf-MEK-ERK pathway. Combination of ERK siRNA knockdown and treatment with the specific MEK inhibitor (U0126) enhanced the cytotoxic effects of the chemotherapy on UC cells. These observations were confirmed in a xenograft nude mouse model. Moreover, activated Raf/MEK/ERK pathway was observed in human bladder UC specimens from patients with chemoresistant status. In conclusion, TSA elicits a synergistic cytotoxic response in combination with chemotherapy via targeting the Raf/MEK/ERK pathway. TSA elicits synergistic cytotoxic response in combination with three DNA-damaging drugs (cisplatin, gemcitabine, and doxorubicin). Activated Raf/MEK/ERK pathway is involved in chemoresistant mechanism of UC. Combining chemotherapeutic agents with HDAC inhibitor (TSA) or with targeting Raf/MEK/ERK pathway is promising to circumvent chemoresistance in UCs.

Indexed as

AnimalsAntineoplastic AgentsApoptosisCell Line, TumorCell SurvivalCisplatinDeoxycytidineDoxorubicinDrug SynergismGemcitabineHistone Deacetylase InhibitorsHumansHydroxamic AcidsMAP Kinase Signaling SystemMice, NudeProtein Kinase InhibitorsAntineoplastic AgentsCisplatinDeoxycytidineDoxorubicinGemcitabineHistone Deacetylase InhibitorsHydroxamic AcidsProtein Kinase InhibitorsProtein KinasesRNA, Small Interferingtrichostatin AChemotherapyDrug resistanceHistone deacetylase inhibitorTrichostatin AUrothelial carcinoma

Identifiers

PMID30288546
OpenAlexW2894792899

What OpenQuestion holds

Textmetadata
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.