科研之友
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摘要
Objective To investigate the potential mechanisms of sulfate sodium (DS) on suppressing human gastric cancer cells (HGC-27) invasion and migration through regulating M2 tumor-associated macrophages (M2-TAMs). Methods (1) In vitro experiment: Differentiation of human monocytes (THP-1) into M0 macrophages was induced by phorbol 12-myristate 13-acetate(PMA). Interleukin 4 (IL-4) and interleukin 13 (IL-13) were used to activate M0 macrophages into M2 macrophages. Immunofluorescence and Western blotting were used to detect the expression of CD163, a specific marker of M2-TAMs. HGC-27 cells were divided into 4 groups, including the control group, DS group, M2 group (co-culture of M2 and HGC-27 cells) and M2+DS group (co-culture of M2 and HGC-27 cells treated with DS). Transwell and scratch tests were performed to detect the invasion and migration ability of HGC-27 cells. (2) Animal experiment: 24 nude mice were randomized into control group (n=12) and DS group (n=12). After 24 h intraperitoneally injecting HGC-27 cells, mice were treated with DS (DS group) or saline (control group) through intraperitoneal injections. Later, mice were sacrificed after 14 days. The number of nodules induced by peritoneal implantation of gastric cancer cells was counted and the omentum tumor tissue was collected to examine CD163 expression levels using immunohistochemistry. (3) Human gastric cancer tissue: Clinical gastric cancer samples were collected; the expression of CD163 and programmed death-ligand 1 (PD-L1) were detected by immunohistochemistry and immunofluorescence. Results (1) In vitro experiment: The expression of CD163 in successfully induced-M2 macrophages was increased; DS could inhibit the polarization of M0 to M2 macrophages; Compared with M2 group, M2+DS group could significantly reduce the invasion and migration ability of HGC-27 cells which was already enhanced by M2-TAMs (P＜0.001). (2) Animal experiment: Compared with Control group, the number and volume of metastatic nodules implanted in the abdominal cavity in DS group were significantly decreased, and the expression of CD163 in omentum tumor tissue in DS group was significantly lower (P＜0.001). (3) In human gastric cancer tissues: The expression of CD163 in poorly differentiated adenocarcinomas was significantly higher than those in well-differentiated adenocarcinomas and adjacent tissues (P<0.05), but there was no significant difference in CD163 expression between well-differentiated adenocarcinomas and adjacent tissues (P＞0.05); The expression of CD163 in PD-L1 positive group was significantly higher than that in PD-L1 negative group (P<0.05). There was a positive correlation between CD163 and PD-L1 expression in human gastric cancer cells (P<0.05, r=0.40). Conclusion Dextran sulfate sodium can inhibit the invasion and migration of human gastric cancer cells by affecting M2 tumor-associated macrophages.
