Paeonol induces the apoptosis of the SGC‑7901 gastric cancer cell line by downregulating ERBB2 and inhibiting the NF‑κB signaling pathway

Fu,Jun; Yu,Luhua; Luo,Jie; Huo,Rui; Zhu,Bing

doi:10.3892/ijmm.2018.3704

Paeonol induces the apoptosis of the SGC‑7901 gastric cancer cell line by downregulating ERBB2 and inhibiting the NF‑κB signaling pathway

Authors:
- Jun Fu
- Luhua Yu
- Jie Luo
- Rui Huo
- Bing Zhu
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Affiliations: Department of Gastrointestinal Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233004, P.R. China, Department of Otolaryngology‑Head and Neck Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233004, P.R. China
Published online on: May 23, 2018 https://doi.org/10.3892/ijmm.2018.3704
Pages: 1473-1483
Copyright: © Fu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The purpose of the present study was to analyze the association between paeonol and the known genes related to gastric cancer (GC) using bioinformatics methods, and to investigate the role of paeonol in the potential impact on the nuclear factor‑κB (NF‑κB) signaling pathway, in order to provide a theoretical basis for further elucidating the effect of paeonol on cancer cells. Cell viability, morphology and apoptosis were detected using an MTT assay, an inverted microscope, and flow cytometry, respectively. The correlation between drugs and genes was analyzed using the Search Tool for Interactions of Chemicals (STITCH) gene‑drug interaction network. The expression levels of related mRNA and proteins were determined using reverse transcription‑quantitative polymerase chain reaction analysis and enzyme‑linked immunosorbent assay. The changes in protein expression were examined using western blot analysis. The correlation network between target genes directly affected by paeonol and known GC genes was determined by analyzing the association between the compounds and genes recorded in the STITCH database. The GC‑related epidermal growth factor receptor 2 (ERBB2) gene was at the core position of the paeonol interaction network and may be an important potential target gene for the effect of paeonol on cancer cells. The effect of paeonol on the viability of the SGC‑7901 GC cell line was detected using an MTT assay, which showed that the inhibitory effect occurred in a time‑ and dose‑dependent manner. The observations of cell morphology demonstrated that the cells were floating, abnormal in shape, had unclear boundaries and were sparse in arrangement following paeonol treatment. Flow cytometry indicated that paeonol significantly accelerated the apoptotic rate of the SGC‑7901 GC cells. The examination of clinical samples suggested that ERBB2 was expressed at a high level in GC samples, and was significantly downregulated following the addition of paeonol. The western blot analysis revealed that downregulating ERBB2 affected the activation of the NF‑κB signaling pathway, thereby upregulating the pro‑apoptotic factor B‑cell lymphoma‑associated X protein. Taken together, paeonol significantly downregulated ERBB2 and inhibited the activation of the NF‑κB signaling pathway, thereby inhibiting the proliferation of SGC‑7901 cells and inducing apoptosis.

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