TY - JOUR
T1 - Modulation of reactive oxygen species in pancreatic cancer
AU - Teoh, Melissa L.T.
AU - Sun, Wenqing
AU - Smith, Brian J.
AU - Oberley, Larry W.
AU - Cullen, Joseph J.
PY - 2007/12/15
Y1 - 2007/12/15
N2 - Purpose: The aim of the present study was to compare the effects of the three different forms of the antioxidant enzyme superoxide dismutase [i.e., manganese superoxide dismutase (MnSOD), copper zinc superoxide dismutase (CuZnSOD), and extracellular superoxide dismutase (EcSOD)] on the malignant phenotype of human pancreatic cancer. Experimental Design: Human pancreatic cancer cell lines were infected with adenoviral vectors containing the cDNAs for three different forms of the antioxidant enzyme SOD. Intratumoral injections of the adenoviral vectors were used in nude mice with human tumor xenografts. Results: Increases in immunoreactive protein and enzymatic activity were seen after infections with the AdMnSOD, AdCuZnSOD, or AdEcSOD constructs. Increased SOD activity decreased superoxide levels and increased hydrogen peroxide levels. Increasing SOD levels correlated with increased doubling time. Cell growth and plating efficiency decreased with increasing amounts of the adenoviral constructs, with the AdCuZnSOD vector having the greatest effect in decreasing in vitro tumor growth. In contrast, inhibiting endogenous SOD with small interfering RNA increased superoxide levels and promoted tumor growth. Of the three SODs, tumors grew the slowest and survival was increased the greatest in nude mice injected with the AdEcSOD construct. Conclusions: Scavenging plasma membrane-generated superoxide may prove beneficial for suppression of pancreatic cancer growth.
AB - Purpose: The aim of the present study was to compare the effects of the three different forms of the antioxidant enzyme superoxide dismutase [i.e., manganese superoxide dismutase (MnSOD), copper zinc superoxide dismutase (CuZnSOD), and extracellular superoxide dismutase (EcSOD)] on the malignant phenotype of human pancreatic cancer. Experimental Design: Human pancreatic cancer cell lines were infected with adenoviral vectors containing the cDNAs for three different forms of the antioxidant enzyme SOD. Intratumoral injections of the adenoviral vectors were used in nude mice with human tumor xenografts. Results: Increases in immunoreactive protein and enzymatic activity were seen after infections with the AdMnSOD, AdCuZnSOD, or AdEcSOD constructs. Increased SOD activity decreased superoxide levels and increased hydrogen peroxide levels. Increasing SOD levels correlated with increased doubling time. Cell growth and plating efficiency decreased with increasing amounts of the adenoviral constructs, with the AdCuZnSOD vector having the greatest effect in decreasing in vitro tumor growth. In contrast, inhibiting endogenous SOD with small interfering RNA increased superoxide levels and promoted tumor growth. Of the three SODs, tumors grew the slowest and survival was increased the greatest in nude mice injected with the AdEcSOD construct. Conclusions: Scavenging plasma membrane-generated superoxide may prove beneficial for suppression of pancreatic cancer growth.
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U2 - 10.1158/1078-0432.CCR-07-0851
DO - 10.1158/1078-0432.CCR-07-0851
M3 - Article
C2 - 18094428
AN - SCOPUS:37549046814
SN - 1078-0432
VL - 13
SP - 7441
EP - 7450
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 24
ER -