Silencing of ECHDC1 inhibits growth of gemcitabine‑resistant bladder cancer cells

  • Authors:
    • Seiji Asai
    • Noriyoshi Miura
    • Yuichiro Sawada
    • Terutaka Noda
    • Tadahiko Kikugawa
    • Nozomu Tanji
    • Takashi Saika
  • View Affiliations

  • Published online on: October 26, 2017     https://doi.org/10.3892/ol.2017.7269
  • Pages:522-527
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Abstract

Combined gemcitabine and cisplatin (GC) treatment is a first line chemotherapy for bladder cancer. However, acquired resistance to GC has been a major problem. To address the mechanism of gemcitabine resistance, and to identify potential biomarkers or target proteins for its therapy, we aimed to identify candidate proteins associated with gemcitabine resistance using proteomic analysis. We established gemcitabine‑resistant human bladder cancer cell lines (UMUC3GR and HT1376GR) from gemcitabine‑sensitive human bladder cancer cell lines (UMUC3 and HT1376). We compared the protein expression of parental and gemcitabine‑resistant cell lines using isobaric tags for relative and absolute quantification (iTRAQ) and liquid chromatography tandem mass spectrometry. Among the identified proteins, ethylmalonyl‑CoA decarboxylase (ECHDC1) expression was significantly increased in both of the gemcitabine‑resistant cell lines compared to the respective parental cell lines. Silencing of ECHDC1 reduced ECHDC1 expression and significantly inhibited the proliferation of UMUC3GR cells. Furthermore, silencing of ECHDC1 induced upregulation of p27, which is critical for cell cycle arrest in the G1 phase, and induced G1 arrest. In conclusion, ECHDC1 expression is increased in gemcitabine‑resistant bladder cancer cells, and is involved in their cell growth. ECHDC1, which is a metabolite proofreading enzyme, may be a novel potential target for gemcitabine‑resistant bladder cancer therapy.

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January 2018
Volume 15 Issue 1

Print ISSN: 1792-1074
Online ISSN:1792-1082

2016 Impact Factor: 1.39
Ranked #68/217 Oncology
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APA
Asai, S., Miura, N., Sawada, Y., Noda, T., Kikugawa, T., Tanji, N., & Saika, T. (2018). Silencing of ECHDC1 inhibits growth of gemcitabine‑resistant bladder cancer cells. Oncology Letters, 15, 522-527. https://doi.org/10.3892/ol.2017.7269
MLA
Asai, S., Miura, N., Sawada, Y., Noda, T., Kikugawa, T., Tanji, N., Saika, T."Silencing of ECHDC1 inhibits growth of gemcitabine‑resistant bladder cancer cells". Oncology Letters 15.1 (2018): 522-527.
Chicago
Asai, S., Miura, N., Sawada, Y., Noda, T., Kikugawa, T., Tanji, N., Saika, T."Silencing of ECHDC1 inhibits growth of gemcitabine‑resistant bladder cancer cells". Oncology Letters 15, no. 1 (2018): 522-527. https://doi.org/10.3892/ol.2017.7269