Objective To investigate effects of phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) and mitogen activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signal pathways on the function of gastric cancer cells and their interaction mechanisms.
Methods PI3K inhibitor LY294002, mTOR inhibitor AZD8055 and MEK inhibitor AZD6244 were used alone and in combination to gastric cancer cell MGC-803. The proliferation of MGC-803 cells was detected with -cholecystokinin8 (CCK8). Cell apoptosis and cycle were detected with flow cytometry. The related protein expressions were detected with Western blot.
Results Both the combined use of LY294002 (at a concentration of 25 μmol/L) with AZD6244 (at a concentration of 125 μmol/L) and AZD8055 (at a concentration of 0.1 μmol/L) with AZD6244 (at a concentration of 125 μmol/L) could significantly inhibit the proliferation of gastric cancer MGC-803 cells, and the two combined treatments both have stronger inhibitory effect than each of the single treatment (P < 0.05 for all). Higher cell apoptosis and proportions of cells arrested in G0/G1 phase were observed in MGC-803 cells with combined treatments of LY294002 with AZD6244 and AZD8055 with AZD6244 than those in the MGC-803 cells with each of single treatment (P < 0.05 for all). Compared with the single treatment of LY294002, AZD8055 or AZD6244, the combined treatments of LY294002 with AZD6244 and AZD8055 with AZD6244 had a more obvious inhibitory effect on the expression of p-AKT, phosphorylated p70 ribosomal protein S6 kinase (p-P70S6K) and p-ERK1/2 (P < 0.05) in MGC-803 cells.
Conclusion PI3K/AKT/mTOR and MAPK/ERK signalling pathways have a synergistic regulatory effect on the growth of gastric cancer cells. The multi-target inhibition of the two signalling pathways could significantly inhibit the growth of cancer cells.
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