Lung cancer is the leading cause of
cancer deaths in both men and women in the United States accounting for about 27% of all
cancer deceases. In our effort to develop newer
therapy for
lung cancer, we evaluated the combinatory antitumor effect of
siRNA targeting
VEGF and the PI3K/mTOR dual inhibitor
PF-04691502. We analyzed the anticancer effect of
siRNA VEGF and
PF-04691502 combination on proliferation, colony formation and migration of A549 and H460
lung cancer cells. Additionally, we assessed the combination treatment antiangiogenic effect on human umbilical vein endothelial cells. Here, we show for the first time that the antiangiogenic
siRNA VEGF potentiates the
PF-04691502 anticancer activity against
non-small-cell lung cancer. We observed a significant (P < 0.05) decrease in cell viability, colony formation, and migration for the combination comparing with the single
drug treatment. We also showed a significant (P < 0.05) enhanced effect of the combination treatment inhibiting angiogenesis progression and tube formation organization compared to the single
drug treatment groups. Our findings demonstrated an enhanced synergistic anticancer effect of
siRNA VEGF and
PF-04691502 combination
therapy by targeting two main pathways involved in
lung cancer cell survival and angiogenesis which will be useful for future preclinical studies and potentially for
lung cancer patient management.