Figure 1 B D DOX ( μ M) C Cell Proliferation (% Con) MCF-7MCF-7/DOX 0 0.1 1 DOX ( μ M) 0.03% 38.79% 0.15% 0.10% 0.20% 0.05% 0 20 40 60 80 100 120 00.110.

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Figure 1 B D DOX ( μ M) C Cell Proliferation (% Con) MCF-7MCF-7/DOX DOX ( μ M) 0.03% 38.79% 0.15% 0.10% 0.20% 0.05% MCF-7MCF-7/DOX ** * A MDA-MB-231 Cell Proliferation (% Con) MCF-7 MCF-7/DOX T47D 0520 DOX (μM) ** MCF-7MCF-7/DOX ― + DOX (1 μ M) ― + PARP (uncleaved) PARP (cleaved) Tubulin

Figure 2 B MCF-7MCF-7/DOX Invasion (No. of cells/HPF) * A CD Lung tumors/ mouse (%) MCF-7MCF-7/DOX * P < uPA MMP-9 MMP-2 MCF-7MCF-7/DOX

A B ControlNS NS398 ( μ M) Cell Proliferation (% Con) Invasion (No. of cells/% control) Figure 3 C Cox-2 Actin MDA-MB-231 MCF-7 MCF-7/DOX T47D Control NS398 (50 μ M) * uPA MMP-9 MMP-2 NS398 ( μ M) D E Migration (No. of cells/% control) * Cox-2 : siRNA SCR

Figure 4 E Gefitinib ( μ M) EGF– + + – – 2 Actin pEGFR Cox-2 EGFR C h EGF EGFR Actin Cox-2 SCR EGFR SCR EGFR : siRNA EGFR Tubulin Cox-2 B A D Gefitinib EGFR Tubulin MDA-MD-231 MCF-7/DOX Invasion (No. of cells/% control) Control MDA-MB-231 MCF-7 MCF-7/DOX T47D ` Gefitinib ( μ M) – 2 Cell Proliferation (% Con) 0 – 2 *

ControlLY Cell Proliferation (% Con) AB C D – + EGF ControlU0126 U0126 ( μ M) – – 5 10 – EGF Actin Cox-2 pERK1/2 Actin Cox-2 ERK 1/2 pERK 1/2 Akt pAkt LY ( μ M) – 10 pAkt LY ( μ M) – + + – – 10 Actin Cox-2 EGF Invasion (No. of cells/% control) * – 10 Invasion (No. of cells/% control) – 10 U0126 ( μ M) Cell Proliferation (% Con) ` – 10 0 * Figure 5 E SCR Cox-2 : siRNA Actin Cox-2 F MMP-9 MMP-2 GAPDH uPA Cox-2SCR : siRNA U0126 Control LY U0126 Control LY MMP-9 MMP-2 GAPDH uPA RT-PCR WB

Figure 6 AB DC SCREP1 EP3 : siRNA EP1 EP3 SCR : siRNA Invasion (No. of cells/% control) SCR EP1 siRNA * EP1 : siRNA SCR MMP-2 MMP-9 uPA β-Actin MCF-7 MCF-7/DOX EP1 EP2 EP3 EP4 PGE 2 – + EP1 EP2 EP3 EP4 β-Actin SCR EP3 siRNA * EP1 EP3 – + – – – – – + – – – – – + + – – – – + PGE 2 17-PT-PGE2 Sulprostone AH6809 GAPDH uPA MMP2 MMP9 E