Exogenous hydrogen sulfide exerts proliferation/anti-apoptosis/angiogenesis/migration effects via amplifying the activation of NF-κB pathway in PLC/PRF/5 hepatoma cells

Zhen,Yulan; Pan,Wanying; Hu,Fen; Wu,Hongfu; Feng,Jianqiang; Zhang,Ying; Chen,Jingfu

doi:10.3892/ijo.2015.2914

Exogenous hydrogen sulfide exerts proliferation/anti-apoptosis/angiogenesis/migration effects via amplifying the activation of NF-κB pathway in PLC/PRF/5 hepatoma cells

Authors:
- Yulan Zhen
- Wanying Pan
- Fen Hu
- Hongfu Wu
- Jianqiang Feng
- Ying Zhang
- Jingfu Chen
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Affiliations: Oncology Center, Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong 524001, P.R. China, Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510700, P.R. China, Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510700, P.R. China, Department of Physiology, Guangdong Medical College, Zhanjiang, Guangdong 524001, P.R. China, Department of Physiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510080, P.R. China, Department of Cardiovasology and Cardiac Care Unit (CCU), Huangpu Division, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510700, P.R. China
Published online on: March 3, 2015 https://doi.org/10.3892/ijo.2015.2914
Pages: 2194-2204

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Abstract

Hydrogen sulfide (H2S) takes part in a diverse range of intracellular pathways and hss physical and pathological properties in vitro and in vivo. However, the effects of H2S on cancer are controversial and remain unclear. The present study investigates the effects of H2S on liver cancer progression via activating NF-κB pathway in PLC/PRF/5 hepatoma cells. PLC/PRF/5 hepatoma cells were pretreated with 500 µmol/l NaHS (a donor of H2S) for 24 h. The expression levels of CSE, CBS, phosphosphorylate (p)-NF-κB p65, caspase-3, COX-2, p-IκB and MMP-2 were measured by western blot assay. Cell viability was detected by cell counter kit 8 (CCK-8). Apoptotic cells were observed by Hoechst 33258 staining assay. The production level of H2S in cell culture medium was measured by using the sulfur-sensitive electrode method. The production of vascular endothelial growth factor (VEGF) was tested by enzyme-linked immunosorbent assay (ELISA). Our results showed that the production of H2S was dramatically increased in the PLC/PRF/5 hepatoma cells, compared with human LO2 hepatocyte cells group, along with the overexpression levels of CSE and CBS. Treatment of PLC/PRF/5 hepatoma cells with 500 µmol/l NaHS (a donor of H2S) for 24 h markedly increased the expression levels of CSE, CBS, p-IκB and NF-κB activation, leading to COX-2 and MMP-2 overexpression, and decreased caspase-3 production, as well as increased cell viability and decreased number of apoptotic cells. Otherwise, the production level of H2S and VEGF were also significantly increased. Furthermore, co-treatment of PLC/PRF/5 hepatoma cells with 500 µmol/l NaHS and 200 µmol/l PDTC for 24 h significantly overturned these indexes. The findings of the present study provide evidence that the NF-κB is involved in the NaHS-induced cell proliferation, anti-apoptisis, angiogenesis, and migration in PLC/PRF/5 hepatoma cells, and that the PDTC against the NaHS-induced effects were by inhibition of the NF-κB pathway.

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