Abstract. The aim of the present study was to determine the antitumor effects of hyperthermic CO 2 (HT-CO 2 )-treated dendritic cell (DC)-derived exosomes (Dex) on human gastric cancer AGS cells. Mouse-derived DCs were incubated in HT-CO 2 at 43˚C for 4 h. The exosomes in the cell culture supernatant were then isolated. Cell proliferation was analyzed using the cell counting kit-8 (CCK-8) assay. Cell apoptosis was observed using flow cytometry, Hoechst 33258 staining and the analysis of caspase-3 activity. In addition, the proliferation of tumor cells was evaluated in xenotransplant nude mice. HT-CO 2 markedly inhibited cell proliferation, as assessed by the CCK-8 assay, and also induced apoptosis in a time-dependent manner, as demonstrated by Annexin V/propidium iodide flow cytometry, caspase-3 activity and morphological analysis using Hoechst fluorescent dye. It was also revealed that HT-CO 2 -treated Dex decreased the expression of heat shock protein 70 and inhibited tumor growth in nude mice. In conclusion, HT-CO 2 exerted an efficacious immune-enhancing effect on DCs. These findings may provide a novel strategy for the elimination of free cancer cells during laparoscopic resection. However, the potential cellular mechanisms underlying this process require further investigation.
IntroductionGastric cancer is the fourth most common cancer worldwide, and the second leading cause of cancer-associated mortalities (1). Important factors underlying the poor prognosis of gastric cancer are recurrence and distant metastases, which may be a result of free cancer cells being shed into the peritoneal cavity during surgical manipulation (2). Therefore, reducing the incidence of recurrence and metastasis is crucial for improving the survival of patients. At present, laparoscopic resection is the first choice of treatment for gastric cancer. This involves the percutaneous injection of CO 2 into the region surrounding the target tumor in order to physically separate the lesion from adjacent structures; however, this approach enhances the spread of free cancer cells into the peritoneal cavity (3).Emerging treatments for gastric cancer with peritoneal carcinomatosis include the use of regional chemotherapy, specifically hyperthermic intraperitoneal chemotherapy, which may improve the prognosis of patients (4). The exposure of tumors to hyperthermic conditions has been revealed to be an effective adjuvant therapy to radiotherapy and chemotherapy for a range of cancers, including locally advanced head and neck cancer (1), melanoma (2), esophageal cancer (3,4), locally advanced cervical cancer (5) and gliomas (6). These results suggest that hyperthermic conditions confer a beneficial effect during laparoscopic resection of gastric cancer (5). CO 2 pneumoperitoneum is used in laparoscopic surgery for the creation of an operative field. Previous data has revealed that compared with ambient temperature CO 2 , hyperthermic CO 2 (HT-CO 2 ) pneumoperitoneum directly inhibits cell proliferation and induces cell apoptosis in gastric an...