Figure 6

MA suppresses pancreatic tumor growth, induces apoptosis, and inhibits the NF-κB-regulated anti-apoptotic gene expression in vivo. (A) MA inhibited pancreatic tumor growth in xenograft mouse model using Panc-28 pancreatic cancer cells in two different doses (10 mg/kg or 50 mg/kg). Both tumor volume and weight significantly decreased in MA-treated groups compared to DMSO control group in a dose-dependent manner. Column, mean; bar, SD (n = 6, **, P < 0.01, ***, P < 0.001 versus control). (B) MA had little effect on mouse body weight. No significant difference between MA-treated groups (10 mg/kg and 50 mg/kg) and the control group. (C) MA inhibited tumor apoptosis and suppressed the expression levels of NF-κB-regulated gene expression in xenograft mouse model. Solid tumor were fixed and embedded with paraffin. The 5 micro m sections were stained with specific TUNEL staining kit (left side), and antibodies for anti-apoptosis proteins, Survivin and Bcl-xl (arrowheads indicate the TUNEL signals, magnification, ×10). (D) A schematic diagram of mechanism by which MA increases pancreatic tumor susceptibility to TNFα. MA or TNFα alone can induce pancreatic cancer cell apoptosis through a caspase-dependant pathway (left). The apoptotic effect of TNFα is attenuated by MA due to NF-κB regulated anti-apoptosis gene expression (right). MA can suppress NF-κB activation therefore enhances TNFα induced apoptosis.