Effects of 17‑allylamino‑17‑demethoxygeldanamycin on the induction of apoptosis and cell cycle arrest in HCT‑116 cells

Zhao,Xuerong; Wang,Jianping; Xiao,Lijun; Xu,Qian; Zhao,Enhong; Zheng,Xin; Zheng,Huachuan; Zhao,Shuang; Ding,Shi

doi:10.3892/ol.2017.6442

Effects of 17‑allylamino‑17‑demethoxygeldanamycin on the induction of apoptosis and cell cycle arrest in HCT‑116 cells

Authors:
- Xuerong Zhao
- Jianping Wang
- Lijun Xiao
- Qian Xu
- Enhong Zhao
- Xin Zheng
- Huachuan Zheng
- Shuang Zhao
- Shi Ding
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Affiliations: Department of Immunology, Chengde Medical University, Chengde, Hebei 067000, P.R. China, Department of Fundamental Research, Chengde Medical University, Chengde, Hebei 067000, P.R. China, The Third Department of Surgery, The Affiliated Hospital of Chengde Medical University, Chengde, Hebei 067000, P.R. China, Cancer Research Center, The First Affiliated Hospital of Liaoning Medical University, Jinzhou, Liaoning 121000, P.R. China, Pharmocology Department, Chengde Medical University, Chengde, Hebei 067000, P.R. China
Published online on: June 21, 2017 https://doi.org/10.3892/ol.2017.6442
Pages: 2177-2185
Copyright: © Zhao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study investigated the effects of HSP90 inhibitor 17‑allylamino‑17‑demethoxygeldanamycin (17‑AAG) on apoptosis and the cell cycle of the HCT‑116 human colon carcinoma cell line, with the aim of elucidating their underlying mechanisms. MTT was used to examine the inhibitory effects of 17‑AAG on the proliferation of HCT‑116 cells at various time points and doses. The cells were stained with Annexin V‑fluorescein isothiocyanate/propidium iodide and evaluated by flow cytometry. The expression of signal transducer and activator of transcription (STAT)3, cyclin D1, cytochrome c (cyt‑c), caspase 9 and caspase 3 at the mRNA and protein level was determined using reverse transcription‑polymerase chain reaction and western blotting. Treatment with 17‑AAG at a concentration of 1.25‑20 mg/l for 24 and 48 h significantly inhibited the proliferation of HCT‑116 cells in a time‑dependent and concentration‑dependent manner. Treatment with 17‑AAG at concentrations of 1.25, 2.5 and 5 mg/l for 48 h significantly induced apoptosis and cell cycle arrest in HCT‑116 cells. Exposure to 17‑AAG at concentrations of 1.25, 2.5 and 5 mg/l for 48 h significantly downregulated the mRNA and protein expression of STAT3 and cyclin D1, but upregulated cyt‑c, caspase 9 and caspase 3 in a concentration‑dependent manner in HCT‑116 cells. Therefore 17‑AAG is able to inhibit cell proliferation, inducing apoptosis and G1 stage cell cycle arrest by downregulating the expression of cyclin D1, and promoting the mitochondria apoptosis by downregulating STAT3 in HCT‑116 cells.

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