Open Access

Transcription activated p73-modulated cyclin D1 expression leads to doxorubicin resistance in gastric cancer

  • Authors:
    • Zhi‑Peng Ji
    • Ling Qiang
    • Jian‑Liang Zhang
  • View Affiliations

  • Published online on: December 15, 2017     https://doi.org/10.3892/etm.2017.5642
  • Pages:1831-1838
  • Copyright: © Ji et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Gastric cancer (GC) is one of the leading types of cancer in terms of mortality cases worldwide. Doxorubicin (Dox), a common chemotherapy drug, is frequently used to treat GC; however, acquired resistance to Dox hinders the chemotherapeutic outcome and causes shorter survival in GC patients. Several Dox‑resistant GC cell lines, including SGC7901, SNU‑1 and SNU‑5 were generated to investigate the mechanism of Dox resistance in GC. Various methods were used to test the response of Dox‑resistant GC cells and parental cells, including flow cytometry, Cell Counting kit‑8 assay, reverse transcription polymerase chain reaction and western blot analysis. In the present study, various Dox‑resistant cells presented reduced apoptosis and cell cycle arrest in response to Dox treatment. Western blot results revealed that cyclin D1 was upregulated in Dox‑resistant cells, whereas inhibition or depletion of cyclin D1 re‑sensitized the resistant cells to Dox treatment, which indicated that the induction of cyclin D1 expression was a result of the Dox resistance in GC cells. Furthermore, it was observed that a transcription activated form of p73 (TAp73), is the upstream modulator of cyclin D1, manipulating the cyclin D1 transcription with the assistance of activator protein 1 (AP‑1). Overall, the present study data provided a rational strategy to overcome the Dox resistance in GC treatment by inhibiting cyclin D1 expression.

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February 2018
Volume 15 Issue 2

Print ISSN: 1792-0981
Online ISSN:1792-1015

2016 Impact Factor: 1.261
Ranked #50/128 Medicine Research and Experimental
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APA
Ji, Z., Qiang, L., & Zhang, J. (2018). Transcription activated p73-modulated cyclin D1 expression leads to doxorubicin resistance in gastric cancer. Experimental and Therapeutic Medicine, 15, 1831-1838. https://doi.org/10.3892/etm.2017.5642
MLA
Ji, Z., Qiang, L., Zhang, J."Transcription activated p73-modulated cyclin D1 expression leads to doxorubicin resistance in gastric cancer". Experimental and Therapeutic Medicine 15.2 (2018): 1831-1838.
Chicago
Ji, Z., Qiang, L., Zhang, J."Transcription activated p73-modulated cyclin D1 expression leads to doxorubicin resistance in gastric cancer". Experimental and Therapeutic Medicine 15, no. 2 (2018): 1831-1838. https://doi.org/10.3892/etm.2017.5642