Helicobacter pylori infection enhances heparanase leading to cell proliferation via mitogen‑activated protein kinase signalling in human gastric cancer cells

Liu,Liping; Zhao,Yongxun; Fan,Guangrui; Shuai,Tiankui; Li,Bin; Li,Yumin

doi:10.3892/mmr.2018.9558

Helicobacter pylori infection enhances heparanase leading to cell proliferation via mitogen‑activated protein kinase signalling in human gastric cancer cells

Authors:
- Liping Liu
- Yongxun Zhao
- Guangrui Fan
- Tiankui Shuai
- Bin Li
- Yumin Li
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Affiliations: The Second Clinical Medical School of Lanzhou University, Lanzhou, Gansu 730030, P.R. China, Department of Surgical Oncology, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China, Department of Critical Care Medicine, The Donggang Branch of The First Hospital of Lanzhou University, Lanzhou, Gansu 730030, P.R. China, Department of Critical Care Medicine, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China, Department of General Surgery, The Second Hospital of Lanzhou University, Key Laboratory of Digestive System Tumors of Gansu Province, Lanzhou, Gansu 730030, P.R. China
Published online on: October 15, 2018 https://doi.org/10.3892/mmr.2018.9558
Pages: 5733-5741

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Abstract

Helicobacter pylori (H. pylori) infection is the most important factor in the development of gastric cancer. Heparanase (HPA) is involved in tissue remodelling and cell migration, which leads to inflammation and tumour metastasis. The current study aimed was to explore whether a H. pylori infection leads to an increase in the level of HPA in gastric cancer and to investigate the specific mechanism underlying this association. Reverse transcription‑polymerase chain reaction and western blotting were used to detect HPA mRNA and protein expression, respectively, in MKN‑45 cells infected by H. pylori, MKN‑45 cells treated with the mitogen‑activated protein kinase (MAPK) inhibitor SB203580 and MKN‑45 cells transfected with small interfering RNA against HPA. MAPK and nuclear factor (NF)‑κB expression were determined by western blotting in the different cells group. Cell Counting Kit‑8, Transwell method, and Scratch and Clone tests were conducted to detect proliferation, invasion, migration and clone formation ability of gastric cancer cells. It was demonstrated that HPA mRNA expression was highest at 6 h post‑infection, while the expression of the HPA protein was highest at 24 h post‑infection in H. pylori‑infected gastric cancer cells. Furthermore, it was demonstrated that H. pylori infection significantly enhanced the expression of MAPK and NF‑κB in MKN‑45 cells at the mRNA and protein levels. SB203580 significantly decreased the expression of NF‑κB in MKN‑45 cells infected with H. pylori. Exposure to SB203580 also significantly decreased the expression of HPA. In the present study, the inhibition of HPA significantly lowered H. pylori‑induced cell proliferation, suggesting that H. pylori infection induces the proliferation of gastric cancer cells through the upregulation of HPA. Taken together, the results of the present study demonstrated that HPA serves a critical role in the development of gastric cancer in H. pylori‑infected cells, which may be an important mechanism through which H. pylori infection leads to gastric cancer. In addition, H. pylori infection promotes the proliferation, invasion and metastasis of gastric cancer cells through the upregulation of HPA expression, and this is likely mediated via the MAPK and NF‑κB signalling pathways. These data suggest that HPA can be used as a therapeutic target in gastric cancer, particularly in cases induced by H. pylori infection.

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