A. AdEcSOD injections decreased MIA PaCa-2 tumor growth in nude mice. The AdEcSOD group had significantly slower tumor growth when compared to the Control and AdEmpty (p < 0.01, n = 5–8/group). On day-17 there was a 6-fold decrease in tumor growth in animals receiving the AdEcSOD vector when compared to Controls and a 4.5-fold decrease in tumor growth when compared to treatment with the AdEmpty vector.
B. AdEcSOD intratumoral injections decreased VEGF staining. Tumor specimens were harvested from AdEmpty treated mice and from mice treated with AdEcSOD at 48 and 96 h after treatment.
C. Relative intensities of VEGF were quantitated using Image J analysis demonstrating decreased VEGF staining 96 h after AdEcSOD injections. Mean ± SEM, n = 3, p < 0.05 vs. AdEmpty.
D. Our working model on how the O2•− produced by NOX2 in pancreatic cancer cells could regulate pancreatic cancer cell growth. Activation of NOX2 leads to an increase in the steady-state level of O2•−. This increase in O2•− leads to an increase in the accumulation of HIF-1α and an increase in associated downstream events, e.g. VEGF secretion and cell growth. The scavenging of extracellular O2•− by EcSOD inhibits the accumulation of HIF-1α accumulation and these events.