| Objective: To explore the effect of interleukin 23 on the development and metastasis of gastric cancer and its potential molecular mechanism.Methods(1) The expression of IL-23 was detected by using immunohistochemial staining and ELISA in each group, including chronic superficial gastritis, chronic atrophic gastritis with intestinal metaplasia and gastric cancer. Meanwhile by using time-resolved fluoroimmunoassay, the level of PG1 in the serum was also assayed. To confirm the relationship between IL-23 and PG1 in chronic atrophic gastritis with intestinal metaplasia tissues or gastric cancer tissues, the Pearson correlation analysis was employed.(2) Using immunohistochemial staining, the expression of IL-23 in GC patients with or without metastasis was determined. The expressions of IL-23, VEGF and MMP9 in serum were detected using ELISA assay.(3) SGC-7901, BGC-823 cell lines were selected as the cell models in vitro and were designed into four groups, namely control group, IL-23-treated group, LY294002-treated group, LY294002 + IL-23-treated group. After treated, the supernatant of each group were collected to detect the expression of MMP9 and VEGF by using ELISA. Besides that, Western blot and fluorogenic quantitative PCR were also employed to test the expression of metastasis-related proteins; The migration of gastric cancer cells were determined by Transwell and wound healing assay.Results:(1) Compared with the chronic superficial gastritis, the expression of IL-23(tissue and serum) was increased in chronic atrophic gastritis with intestinal metaplasia and gastric cancer. And the level of PG1 was decrease in chronic atrophic gastritis with intestinal metaplasia and gastric cancer when compared with chronic superficial gastritis. As shown in the result of Pearson correlation analysis, there was a negative relationship between serum IL-23 and PG1 in chronic atrophic gastritis with intestinal metaplasia or gastric cancer patients.(2) It was found that the expression of IL-23 in the tissues of gastric cancer patients with and without metastasis was significant enhanced when compared with pericarcinous tissue(P<0.05). And it was also found that the expression of IL-23 graded increase in gastric cancer patients with metastasis compared with gastric cancer patients without metastasis(P<0.05). The expressions of IL-23, MMP9, VEGF in the serum of gastric cancer patients was significant enhanced when compared with control group(P<0.05). And it was also found that the expressions of IL-23, MMP9, VEGF in the serum of gastric cancer patients with metastasis higher than that in without metastasis(P<0.05). There was a positive relationship between serum IL-23 and MMP9, VEGF in gastric cancer patients.Together with the information of immunohistochemical staining and the basic clinical information of each patient, it was indicated that IL-23 was associated with TNM stage, lymphatic metastasis and there was no links with patients’ age and gender.(3)The level of VEGF, MMP9(mRNA and protein) were enhanced and the level of E-cadherin(mRNA and protein) were decreased when treated with IL-23 compared with control group. And the migration assay(wound healing and Transwell assay) also showed that IL-23 increased the migration of gastric cancer cell compared with control group. However, when treated with LY294002, the results above were reversed.Conclusion:(1) There were a high level of IL-23 in the serum and tissue of chronic atrophic gastritis with intestinal metaplasia and gastric cancer patients and there was a negative relationship between IL-23 and PG1.(2) The level of IL-23 was high in the tissue of gastric cancer and it was associated with the gastric cancer metastasis.(3) The expression of VEGF, MMP9 were high in the serum of gastric cancer patients and there was a positive relationship between IL-23 and VEGF, MMP9.(4) IL-23 enhance the expression of VEGF, MMP9(mRNA and protein) and decrease the expression of E-cadherin(mRNA and protein) in gastric cancer cell SGC-7901 and BGC-823.(5) IL-23 promotes the migration of SGC-7901 and BGC-823 via PI3K/Akt signaling pathway. |
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