Objective To investigate the synergistic effect of phosphalyl inositol 3-kinase protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) and mitogen activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathways on gastric cancer cell growth.
Methods Different concentrations of PI3K/Akt/mTOR and MAPK/ERK signaling pathways inhibitor rapamycin and PD98059 were used alone and in combination to SGC-7901 cells, respectively. The proliferation of SGC-7901 cells was detected with cholecystokinin-8 (CCK8). The mRNA expressions of key genes were detected with real time quantitative polymerase chain reaction (RT-qPCR). The expressions of related proteins were detected with Western blot. Cell cycles and apoptosis were detected with flow cytometry.
Results Both the single administration of rapamycin (at dosages of 12.5, 25, 50, 100, 150, and 200 nmol/L) and PD98059 (at dosages of 25, 50, 100, 150, 200, 300, and 400 μmol/L) could inhibit the growth of SGC-7901 cells; so did the combined administration of the two agents and the inhibitory effect of the combined administration was stronger than that of the single agent (P < 0.05). The combined administration of rapamycin and PD98059 exerted a much stronger inhibitive effect on the mRNA expressions of AKT, mTOR, mitogen activated protein kinase kinase (MEK), ERK and the protein expressions of p-AKT, p-mTOR, p-MEK1/2 and p-ERK1/2 than the single administration of one of the two agents (P < 0.05 for all); higher proportions of cells arrested at G0/G1 phase and apoptosis cells were also observed for the SGC-7901 cells with combined administration than those for the SGC-7901 cells with the single administration.
Conclusion PI3K/Akt/mTOR and MAPK/ERK signaling pathways have a synergistic effect on the growth of gastric cancer cells.
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