Fig. 4

Gambogic acid (GA) reduced ribonucleotide reductase subunit-M2 (RRM2) expression through inhibition of the ERK signaling pathway. a PANC-1 and BxPC-3 cells were treated with 0.0, 0.5, 1.0, 1.5, and 2.0 μM, respectively, for 24 h. The protein levels of p-ERK, ERK, p-AKT, and AKT were detected using western blot analysis. b PANC-1 and BxPC-3 cells were treated with 2 μM GA for 0, 1, 6, 12, and 24 h, respectively. The protein levels of p-ERK, ERK, p-AKT, and AKT were detected using western blot analysis. c, d PANC-1 and BxPC-3 cells were treated with 0, 0.5, 1, 1.5, and 2 μM, respectively, for 24 h. The mRNA levels of RRM1 and RRM2 were detected by q-PCR. e, f PANC-1 and BxPC-3 cells were treated with 2 μm GA for 0, 1, 6, 12, and 24 h, respectively. The mRNA levels of RRM1 and RRM2 were detected by q-PCR. g PANC-1 and BxPC-3 cells were treated with 0, 1, 1.5, 2, and 4 μM GA for 24 h, respectively. The protein levels of RRM1 and RRM2 were detected using western blot analysis. h PANC-1 and BxPC-3 cells were treated with 1 nM of the ERK inhibitor ulixertinib for 24 h. The protein levels of p-ERK, ERK, and RRM2 were detected using western blot analysis. Data are presented as mean ± SD (n = 3); * indicates P < 0.05; ** indicates P < 0.01; *** indicates P < 0.001