Abstract:

Objective To investigate the effect of propofol on the proliferation, migration and invasion of human gastric cancer cells and its molecular mechanism. Methods The cell viabilities of human gastric MGC-803 and HGC-27 cells under different concentration of propofol were detected by methyl thiazolyl tetrazolium (MTT) method. MGC-803 cells were divided into control group and propofol group. Hoechst 33258 staining and electron microscopy were used to detect the apoptosis rates of the two groups of cells. Transwell experiment was used to detect the migration and invasion rates of the two groups of cells. The cells were then divided into control group, propofol group and propofol + miR-195i group. Real-time fluorescent quantitative PCR (qRT-PCR) was used to detect the relative expression of miR-195 in the cells. Western blotting was used to detect the expressions of Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway proteins. Results At 24 h, the cell viabilities of MGC-803 cells under the action of 0, 1, 5, 10 and 20 mg/L propofol respectively were (100.00±4.96)%, (94.63±3.15)%, (77.38±6.73)%, (63.82±8.42)% and (35.94±7.01)%, with a statistically significant difference (F=5.148, P<0.001). The cell viabilities of MGC-803 cells under the action of 5, 10 and 20 mg/L propofol were decreased significantly compared to that under the action of 0 mg/L propofol (all P<0.05). At the same time, the effects of propofol for 48 and 72 h could also significantly reduce the viabilities of MGC-803 cells. Similar results were also detected in HGC-27 cells. The results of Hoechst 33258 staining showed that the percentage of positive cells in the control group was (3.73±1.81)%, and that in the propofol group was (25.44±1.05)%, with a statistically significant difference (t=6.415, P<0.001). The results of electron microscopy showed that the apoptosis rate in the control group was (4.60±1.36)%, and that in the propofol group was (28.15±1.99)%, with a statistically significant difference (t=10.729, P<0.001). Transwell results showed that the cell migration rate in the control group was (53.94±4.62)%, and that in the propofol group was (21.28±3.98)%; the cell invasion rate in the control group was (62.38±6.75)%, and that in the propofol group was (33.81±4.92)%, and there were statistically significant differences (t=4.628, P<0.001; t=6.418, P<0.001). qRT-PCR results showed that the relative expressions of miR-195 in the control group, propofol group and propofol + miR-195i group were 0.58±0.09, 1.24±0.22 and 0.63±0.16, with a statistically significant difference (F=1.547, P=0.001). miR-195 expression was increased significantly in the propofol group compared to the control group (P<0.001). Compared with the propofol group, miR-195 expression in the propofol + miR-195i group was decreased significantly (P<0.001). Western blotting results showed that the relative expressions of phosphorylase Janus kinase 1 (p-JAK1) protein in the control group, propofol group and propofol + miR-195i group were 1.18±0.36, 0.27±0.08 and 0.58±0.11; the relative expressions of phosphorylase signal transducer and activator of transcription 3 (p-STAT3) protein in the three groups were 0.83±0.16, 0.21±0.07 and 0.72±0.13, and there were statistically significant differences (F=1.655, P<0.001; F=2.520, P<0.001). The expressions of p-JAK1 and p-STAT3 protein in the propofol group were decreased significantly compared to the control group (P<0.001; P=0.001). The expressions of p-JAK1 and p-STAT3 protein in the propofol + miR-195i group were increased significantly compared to the propofol group (P=0.003; P=0.004). Conclusion Propofol can inhibit the cell proliferation, migration and invasion of gastric cancer MGC-803 cells, and promote its apoptosis. Its mechanism may be related to the promotion of miR-195 expression and inhibition of JAK/STAT signal pathway activity.

Key words: Stomach neoplasms, Propofol, Cell proliferation, Neoplasm invasiveness, miR-195