Direct injection of Aki1 siRNA into the pleural cavity of a DMM orthotopic mouse model dramatically decreases tumor formation. 211H transfected the Eluc/EGFP gene cells (211H/Eluc; 1 × 106 cells per 100 mL of PBS) and were injected into the right pleural cavity of 5-week-old male SCID mice. On day 7 after cell inoculation, 100 μg of either scramble or Aki1 siRNA complexed with invivofectamine was injected into the right pleural cavity. A, luminescence was evaluated twice per week from day 2 to day 19 after cell inoculation. Bars, SE is shown for groups of 8 mice; *, P < 0.05 by one-way ANOVA. B, the appearance of representative mice is shown. C, the harvested tumors, which are on day 7 after injection of siRNA complex, were examined for Aki1 and phosphorylated CREB1 by Western blotting analysis.