Synergistic effects of GDC0941-AZD6244 combination therapy on cell viability and proliferation.

<p>BxPC-3 (A) and MIA PaCa-2 cells (B) were treated with GDC0941 alone, AZD6244 alone or GDC0941-AZD6244 in combination. Results were analyzed according to the Chou-Talalay method [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0077243#B18" target="_blank">18</a>]. The combination index (CI) values were calculated by using CalcuSyn software. PANC-1 (C) and Capan-2 cell line (D) were treated with GDC0941 at 400 nM, AZD6244 at 200 nM or combination. * p value <0.05 compared with control or single agent alone.</p

Effects of GDC0941 and AZD6244 on PI3K/AKT and MEK/ERK pathways of MIA PaCa-2 and PANC-1 cell lines.

<p>Both MIA PaCa-2 and PANC-1 cells were treated with 400 nm GDC0941, 200 nM AZD6244 or a combination at these doses for 24 hours. Cell proteins were then harvested to detect p-AKT(S473)/AKT, p-ERK(T202/Y204)/ERK, p-S6(S240/244)/S6 and p-4E-BP1(S65)/4E-BP-1.</p

Cell viability effect of GDC0941 and AZD6244 in BxPC-3, MIA PaCa-2, PANC-1 and Capan-2 pancreatic cancer cell lines.

<p>Cells were treated with varying concentrations of GDC0941 (A) or AZD6244 (B) alone for 72 hours. Doses ranged from 1 nM to 10 µM.</p

Effects of GDC0941 and AZD6244 therapy on cell apoptosis in pancreatic cancer cell lines.

<p>Pancreatic cancer cell lines were treated with GDC0941 alone, AZD6244 alone or GDC0941-AZD6244 in combination for 72 hours. Cell apoptosis was detected by flow cytometry. A, B: combinations vs. untreated groups (*p values <0.05), combinations vs. single agents (*p values <0.05), single agents vs. untreated groups (*p values <0.05). C, D: combinations vs. untreated groups (*p value <0.05) and combinations vs. single agents (*p value <0.05).</p

Effects of GDC0941 and AZD6244 on BxPC-3 xenograft model.

<p>A: 1×10⁶ BxPC-3 pancreatic cancer cells were injected s.c. into the right flank of female nude mice. Mice received vehicle (0.5% methylcellulose /0.2% Tween-20), 50 mg/kg GDC0941 QD, 25 mg/kg AZD6244 BID, or 50 mg/kg GDC0941 QD plus 25 mg/kg AZD6244 BID orally for 18 days. Data are presented as mean ± SE. *p values were determined by unpaired t-test. B: Kaplan-Meier survival curves of xenografts receiving vehicle, GDC0941 alone, AZD6244 alone and GDC0941-AZD6244 in combination.</p

Effects of GDC0941-AZD6244 combination therapy on PI3K/AKT and MEK/ERK pathways.

<p>All four pancreatic cancer cell lines were treated with the GDC0941-AZD6244 combination for 24 hours, Cell lysates were then harvested to detect p-AKT (S473)/AKT, p-ERK (T202/Y204)/ERK, p-S6 (S240/244)/S6 and p-4E-BP1 (S65)/4E-BP1.</p