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AIM To detect the mechanisms of Helicobacter pylori (H. pylori) infection in the invasion and metastasis of gastric cancer (GC). METHODS Specimens from 99 patients with GC were collected. The correlation among H. pylori infection, heparanase (HPA) and mitogen-activated protein kinase (MAPK) expression, which was determined by immunohistochemistry, and the clinical features of GC was analysed using SPSS 22.0. Overall survival (OS) and relapse-free survival (RFS) of GC patients were estimated by the Kaplan-Meier method. Independent and multiple factors of HPA and MAPK with prognosis were determined with COX proportional hazards models. HPA and MAPK expression in MKN-45 cells infected with H. pylori was analysed using Western blot. RESULTS H. pylori infection was observed in 70 of 99 patients with GC (70.7%), which was significantly higher than that in healthy controls. H. pylori infection was related to lymph metastasis and expression of HPA and MAPK (P < 0.05); HPA expression was relevant to MAPK expression (P = 0.024). HPA and MAPK expression in MKN-45 cells was significantly upregulated following H. pylori infection and peaked at 24 h and 60 min, before decreasing (P < 0.05). SB203580, an inhibitor of MAPK, significantly decreased HPA expression. HPA was related to lymph metastasis and invasive depth. HPA positive GC cases and H. pylori positive GC cases showed poorer prognosis than HPA negative cases (P < 0.05). COX models showed that the prognosis of GC was connected with HPA expression, lymph metastasis, tissue differentiation, and invasive depth. CONCLUSION H. pylori may promote the invasion and metastasis of GC by increasing HPA expression that may associate with MAPK activation, thus causing a poorer prognosis of GC.

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.

The effects of hepatic stellate cells (HSCs) on tumorigenicity of HCC have been previously reported. However, the detailed mechanisms responsible for these effects remain unclear. In this study, we investigated the effects of HSCs on cisplatin-induced apoptosis in human hepatoma HepG2 cell lines. HepG2 cells were treated with cisplatin alone or co-cultured with LX-2 cells 3 days before incubation with cisplatin. Cisplatin causes apoptosis in HepG2 cells and LX-2 cells protect HepG2 cells from death. The protection of LX-2 cells against cisplatin-induced cytotoxicity in HepG2 cells appeared to be related to the inhibition of apoptosis, as determined by cytotoxicity assay and nuclear staining analysis. p53 and Bax mRNA levels were elevated, and cell cycle arrest was produced after cisplatin treatment. LX-2 cells suppressed this elevation of p53 and Bax as well as the cell cycle arrest induced by cisplatin, when compared with those of the treated cells with cisplatin alone. The LX-2 cells pretreatment inhibited the cisplatin-induced apoptosis, which was related with the incomplete blockage in p53 activation. In summary, the results of our present study demonstrate that HSCs protect HepG2 cells against cisplatin-induced apoptosis and its protective effects occur via inhibiting the activation of p53, which is of critical importance for enhanced understanding of fundamental cancer biology.