Propranolol suppresses the proliferation and induces the apoptosis of liver cancer cells

Wang,Fang; Liu,Hui; Wang,Fengmei; Xu,Ruicheng; Wang,Peng; Tang,Fei; Zhang,Xu; Zhu,Zhengyan; Lv,Hongmin; Han,Tao

doi:10.3892/mmr.2018.8476

Propranolol suppresses the proliferation and induces the apoptosis of liver cancer cells

Authors:
- Fang Wang
- Hui Liu
- Fengmei Wang
- Ruicheng Xu
- Peng Wang
- Fei Tang
- Xu Zhang
- Zhengyan Zhu
- Hongmin Lv
- Tao Han
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Affiliations: The Third Central Clinical College of Tianjin Medical University, Tianjin 300170, P.R. China, Tianjin Institute of Hepatobiliary Disease, Tianjin 300170, P.R. China, Department of Gastroenterology and Hepatology of Tianjin Third Central Hospital, Tianjin 300170, P.R. China, Tianjin Key Laboratory for Biomarkers of Occupational and Environmental Hazard, Tianjin 300170, P.R. China
Published online on: January 24, 2018 https://doi.org/10.3892/mmr.2018.8476
Pages: 5213-5221
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

An increasing amount of evidence indicates that the inhibition of β adrenergic signaling can result in the inhibition of tumor growth. However, the role of propranolol in liver cancer and the underlying mechanism remain to be elucidated. The present study aimed to investigate the role of propranolol in liver cancer cell lines and provide evidence for further clinical study. Propranolol was added at different concentrations to HepG2 and HepG2.2.15 liver cancer cells and HL‑7702 normal human liver cells. The proliferation of the cell lines was monitored by live‑cell imaging at a range of time intervals. Immunofluorescence using DAPI and Hoechst 33342/propidium iodide (PI) staining, Annexin V‑FITC/PI double‑staining flow cytometry, western blotting and reverse transcription‑quantitative polymerase chain reaction were used to investigate the effect of propranolol on liver cancer cell apoptosis. The proliferation of HepG2 and HepG2.2.15 cells was inhibited by 40 and 80 µmol/l propranolol. However, the proliferation of HL‑7702 cells was not affected by <160 µmol/l propranolol. Propranolol treatment decreased the expression of adrenergic receptor β‑2 to a greater extent than adrenergic receptor β‑1, and induced apoptosis in the liver cancer cells. The apoptotic rates of HepG2 and HepG2.2.15 cells increased following treatment with propranolol, while the apoptotic rate of HL‑7702 cells was not affected. Propranolol promoted poly (ADP‑ribose) polymerase cleavage and decreased the expression of full‑length caspase‑3 in liver cancer cell lines; it induced S‑phase arrest in HepG2 and HepG2.2.15 cell lines, while HL‑7702 cells were arrested at the G0/G1 phase of the cell cycle. Thus, it was demonstrated that propranolol inhibited proliferation, promoted apoptosis and induced S-phase arrest in HepG2 and HepG2.2.15 cells.

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