Trichostatin A inhibits proliferation of PC3 prostate cancer cells by disrupting the EGFR pathway

Zhang,Hong; Zhao,Xin; Liu,Hongbo; Jin,Hui; Ji,Youbo

doi:10.3892/ol.2019.10384

Trichostatin A inhibits proliferation of PC3 prostate cancer cells by disrupting the EGFR pathway

Authors:
- Hong Zhang
- Xin Zhao
- Hongbo Liu
- Hui Jin
- Youbo Ji
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Affiliations: Department of Clinical Medicine, Changchun Medical College, Changchun, Jilin 130031, P.R. China, Department of Pain Medical Center, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China
Published online on: May 21, 2019 https://doi.org/10.3892/ol.2019.10384
Pages: 687-693
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Prostate cancer (PC) is the most common type of malignancy to exist in men within developed countries. Androgen deprivation therapy is performed for metastatic and advanced PC. However, the majority of cases of prostate cancer become refractory during therapy, leading to castration‑resistant PC (CRPC). Histone deacetylases (HDACs) are key factors in regulating gene transcription and have been associated with cancer development. In the present study the small molecule inhibitor trichostatin A (TSA), which targets HDACs, was demonstrated to inhibit the proliferation of CRPC PC3 cells by disrupting the epidermal growth factor receptor (EGFR)‑STAT3 pathway. The expression of EGFR and STAT3 was downregulated following TSA treatment, and cell cycle arrest was induced by downregulating the expression of cyclin D1 and CDK6, and via retinoblastoma protein phosphorylation. Furthermore, the transcription of cyclin D1 and CDK6 was suppressed by TSA. Apoptosis of PC3 cells treated with TSA was also investigated, and it was revealed that TSA induced apoptosis by upregulating BAX and downregulating BCL‑2. The combination of TSA with doxorubicin exerted a synergistic inhibitory effect on PC3 cell proliferation through the induction of apoptosis. The results of the present study revealed a promising epigenetic‑based therapeutic strategy that could be implemented in cases of CRPC.

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