Abstract:
Objective To investigate the effects of PI3K pathway inhibition on the expression and distribution of P27 and phosphorylated P27(p-P27) in the BGC-823 gastric cancer cell line.
Methods The cell line BGC-823 was cultivated and treated with LY294002, a PI3K pathway inhibitor.The cell cycle was determined using flow cytometry.The total cell, cytoplasmic, and nuclear expression of P27, p-P27(Thrl87), p-P27(Thrl57), and p-P27(SerlO) were analyzed by Western blot analysis.
Results Inhibition of the PI3K pathway arrested cell cycle progression in the G1 phase(treated cells vs.control cells was 83.9%vs.67.6%, P < 0.01).The total cell, cytoplasmic, and nuclear expression of P27 was significantly increased in the treated group compared with those in the control group(P < 0.01, P < 0.01, and P < 0.01, respectively).The total cell, cytoplasmic, and nuclear expression of p-P27(Ser10) was significantly decreased in the treated group compared with that in the control group(P < 0.01, P < 0.01, and P < 0.01, respectively). The total cell and cytoplasmic expression of p-P27(Thr157) was significantly decreased in the treated group compared with that in the control group(P < 0.01 and P < 0.01, respectively).The nuclear expression of p-P27(Thr157) was decreased, but it did not reach statistical significance(P= 0.482).The total cell and cytoplasmic expression of p-P27(Thr187) was decreased but the nuclear expression was increased.However, the differences were not statistically significant(P= 0.254, P= 0.70, and P= 0.223, respectively).
Conclusion Inhibiting the PI3K pathway in the BGC-823 gastric cancer cell line upregulates P27 expression and downregulates p-P27 expression. Moreover, the cytoplasmic and nuclear distribution of P27 and p-P27 were altered.Inhibiting the PI3K pathway induces G 1 arrest and triggers the apoptosis of gastric cancer cells.