Molecular, biological characterization and drug sensitivity of chidamide‑resistant non‑small cell lung cancer cells

Luo,Song'e; Ma,Kai; Zhu,Hongxia; Wang,Shuren; Liu,Mei; Zhang,Weina; Liang,Shufang; Xu,Ningzhi

doi:10.3892/ol.2017.7060

Molecular, biological characterization and drug sensitivity of chidamide‑resistant non‑small cell lung cancer cells

Authors:
- Song'e Luo
- Kai Ma
- Hongxia Zhu
- Shuren Wang
- Mei Liu
- Weina Zhang
- Shufang Liang
- Ningzhi Xu
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Affiliations: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan 610041, P.R. China, Laboratory of Cell and Molecular Biology & State Key Laboratory of Molecular Oncology, Cancer Institute & Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China
Published online on: September 26, 2017 https://doi.org/10.3892/ol.2017.7060
Pages: 6869-6875

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Abstract

Chidamide, a histone deacetylase (HDAC) inhibitor, has been applied in clinical trials for various types of hematological and solid tumors. Although acquired resistance is common in chemotherapy, the mechanism of resistance to chidamide is poorly characterized. The goal of the present study was to explore, in detail, the mechanism for the induced resistance to chidamide, and investigate a potential cross‑resistance to other chemotherapeutic drugs. A549 cells were exposed to gradually increasing chidamide concentrations to establish a chidamide‑resistant non‑small cell lung cancer cell line (A549‑CHI‑R). The IC50 for chidamide, the proliferation inhibition rate, the total HDAC activity and the HDAC protein level were determined by an MTT assay, colony formation, a fluorometric HDAC activity assay and western blotting, respectively. Overexpression of the HDAC1 gene and HDAC1 gene‑knockdown were achieved via plasmid transfection. A549‑CHI‑R cells demonstrated increased resistance to chidamide (8.6‑fold). HDAC1 protein degradation was inhibited and HDAC activity was significantly higher in the A549‑CHI‑R cells relative to the parental A549 cells. A549‑CHI‑R cells demonstrated cross‑resistance to paclitaxel, vinorelbine and gemcitabine, but not to cisplatin (CDDP) or 5‑fluorouracil (5‑FU). These results indicated that HDAC1 may be associated with resistance to chidamide, and HDAC1 may therefore be a predictive marker for chidamide sensitivity in cancer. In addition, A549‑CHI‑R cells remained sensitive to 5‑FU and CDDP, indicating a potential strategy for cancer therapy.

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