DNA methyltransferase 3a modulates chemosensitivity to gemcitabine and oxaliplatin via CHK1 and AKT in p53‑deficient pancreatic cancer cells

Jing,Wei; Song,Na; Liu,Yunpeng; Qu,Xiujuan; Hou,Kezuo; Yang,Xianghong; Che,Xiaofang

doi:10.3892/mmr.2017.7923

DNA methyltransferase 3a modulates chemosensitivity to gemcitabine and oxaliplatin via CHK1 and AKT in p53‑deficient pancreatic cancer cells

Authors:
- Wei Jing
- Na Song
- Yunpeng Liu
- Xiujuan Qu
- Kezuo Hou
- Xianghong Yang
- Xiaofang Che
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Affiliations: Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China, Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China, Department of Pathology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China
Published online on: October 27, 2017 https://doi.org/10.3892/mmr.2017.7923
Pages: 117-124
Copyright: © Jing et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The aberrant expression of DNA methyltransferases (DNMTs) has been considered to be associated with pancreatic carcinogenesis and progression. DNMT3a is widely involved in cell proliferation and cell cycle progression in pancreatic ductal adenocarcinoma (PDAC) cells. However, its regulation of chemosensitivity to gemcitabine (GEM) and oxaliplatin (OXA) in p53‑deficient PDAC remains unclear. In the present study, the effect and mechanisms of DNMT3a on GEM and OXA chemosensitivity in p53‑deficient PDAC cells were investigated using MTT assay, cell cycle analysis, apoptosis analysis and western blotting. The treatment of GEM and OXA induced S phase arrest by DNA damage, and enhanced the activation of the AKT signaling pathway in Panc‑1 cells. Downregulation of DNMT3a increased the chemosensitivity to both GEM and OXA in Panc‑1 cells. DNMT3a depletion distinctly abolished S phase arrest induced by GEM and OXA. Further research demonstrated that activation inhibition of CHK1 and AKT, as well as an increase in apoptosis, were involved in DNMT3a‑mediated chemosensitivity to GEM and OXA. Taken together, these data demonstrated that DNMT3a serves a crucial role in the regulation of chemosensitivity to GEM and OXA, and suggests a promising therapeutic target for p53‑deficient PDAC.

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