Effects of CO2 pneumoperitoneum on proliferation, apoptosis, and migration of gastrointestinal stromal tumor cells.

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The purpose of the study was to investigate the proliferation and migration capability of human gastrointestinal stromal tumor line GIST-T1 after exposure to different pressures and times of CO2 pneumoperitoneum. We established simulated CO2 pneumoperitoneum environment in vitro and divided the human GIST cell GIST-T1 into open control group, 8mmHg CO2 pneumoperitoneum treatment group and 15mmHg CO2 pneumoperitoneum treatment group. Each group was divided into two subgroups respectively cultured for 1h and 3h. pH value of cell culture, cell growth curve, and cell cycle distribution of each group was measured. By application of scratch healing tests and Transwell chamber experiments, mobility ratio and number of cells through 8µm membranes were measured to assess the migration ability of cells in each group after intervention. Cell culture pH value of each subgroup in CO2 group decreased significantly after exposed in CO2 pneumoperitoneum (P < 0.01). The proliferation of GIST-T1 cells in 15mmHg CO2 group was significantly inhibited early (1-2 days) (P < 0.05) and the proliferation of GIST-T1 cells in 8mmHg CO2 1h subgroup and 15mmHg CO2 1h subgroup was increased significantly late (4-6 days) (P < 0.05) after the interventions of CO2 pneumoperitoneum. The percentage of cells in G0-G1 phase increased, the percentage of S phase cells decreased (P < 0.01) in 1-h subgroup and 3-h subgroup of 15mmHg CO2 group 24h after exposure to CO2. The percentage of cells in S phase increased in 1-h subgroup of 8mmHg CO2 group and decreased in 3-h subgroup of 15mmHg CO2 group 72h after exposure to CO2. In the Transwell chamber experiment, the cell number through 8-µm membrane increased significantly (P < 0.01) in 3-h subgroup of CO2 group compared to that in 3-h subgroup of control group. The routine pressure and duration of CO2 pneumoperitoneum used in clinic did not promote the proliferation of gastrointestinal stromal tumors, but had a potential risk of increasing postoperative recurrence and distant metastasis.