| ObjectiveTo investigate the effects of carbon dioxide (CO2) pneumoperitoneum environment on the biological behavior and chemotherapy drug sensitivity of human ovarian carcinoma cell (SKOV3) xenografts in nude mice.MethodsAn artificial pneumoperitoneum model was established. SKOV3 cells were exposed to laparoscopic CO2 pneumoperitoneum environment at 12 mmHg CO2 pressure for lh(a group)or 3h(b group). Cells in the control group (c group) were cultured in a standard CO2 incubator. Three groups of cells were collected and beat into the cell suspensions. The paired nude mice were randomly divided into A, B, C three groups (n= 10 pairs). Cell suspensions(0.1mL) were inoculated into the left scapular subcutaeous of nude mice in each group. After the tumors had formed apparently three days later, nude mice(10 pairs) were randomly divided into two groups again. A1,B1,C1(DDP group) were injected cisplatin intraperitoneally (5mg/kg,0.5mL,qw×3); A2,B2,C2 (non-treatment groups) were injected saline intraperitoneally (0.5mL,qw×3). Tumor growth was detected and the growth curve was drawn. All nude mice were sacrificed by dislocation and dissected on the following day of drug withdrawal. The exploration of abdominal and pelvic cavity was performed successively. Whether metastasis in the organs,ascites and lymphatic metastasis existed or not were recorded. Tumor tissues were peeled completely. Tumor volume and weight were measured accurately. The expressions of proliferating cell nuclear antigen (PCNA), vascular endothelial growth factor (VEGF), adhesion molecule (CD44v6) and nonmetastasis gene (nm23-H1) in xenograft tumors were analyzed by immunohistochemical staining. All data were analyzed statistically by using SPSS 11.5 statistics software. Tumor volume and weight were denoted by x±s. One-way ANOVA, factorial design ANOVA, LSD test, Kruskal-Wallis H test, Mann-Whitney U test and Spearman correlation analysis were used. P＜0.05 was selected as significant standard.Results①After hypodermic inoculation for 10 days, the tumors formed apparently. The rate of tumor formation was 100%. Hemorrhage and necrosis can be seen in the tumors exposed to CO2 pneumoperitoneum environment.②The proliferation rate of xenograft tumors in the CO2 treated groups was higher than that in the control group (P＜0.01), and that treated for 3 hours was higher than for 1 hour (P＜0.01).③Tumor sensitivity to DDP in the CO2 treated groups decreased compared with the control group (P＜0.01). There was an interaction between carbon dioxide and cisplatin(P＜0.05).④After explored abdominal and pelvic cavity, metastasis,ascites and lymphatic metastasis weren't observed.⑤The expressions of PCNA and VEGF in xenograft tumors were significantly higher in the CO2 treated groups than that in the control group (P＜0.01) and lower in the treatment groups than that in the non-treatment groups (P＜0.05). But there was no significant difference between the two CO2 treated groups in the expressions of PCNA and VEGF (P＞0.05). There was a positive correlation between the expressions of PCNA and VEGF(rs=0.792, P＜0.01). There was no significant difference between the groups in the expression of CD44v6 and nm23-H1(P＞0.05). There was a negative correlation between the expressions of CD44v6 and nm23-H1(rs=-0.791, P＜0.01)ConclusionsCarbon dioxide promotes the proliferation of human ovarian carcinoma cell (SKOV3) xenografts in BALB/c nude mice, decreases tumor sensitivity to DDP and has no effect on tumor metastasis.Significance①Carbon dioxide promotes the proliferation of human ovarian carcinoma cell (SKOV3) xenografts in BALB/c nude mice, and the promotion is related to time. These conclusions suggest that skillfully master laparoscopy is the key to reduce the adverse reaction of carbon dioxide.②Intraperitoneal chemotherapy can inhibit tumor growth. This conclusion suggests that intraperitoneal chemotherapy is the key to reduce the adverse reaction of carbon dioxide.
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