AbstractBACKGROUND:The 5‐year survival rate for patients with pancreatic cancer is <5%, and it is always resistant to the current chemoradiotherapy. Therefore, new, effective agents for the treatment of pancreatic cancer are urgently needed. The promising strategy of cancer‐targeting gene virotherapy (CTGVT) has demonstrated great anticancer potential. The objective of the current study was to determine whether 1 CTGVT approach, oncolytic virus (OV)‐harboring lipocalin‐2, is capable of treating pancreatic cancer.METHODS:Tissue microarrays were constructed to detect the expression of lipocalin‐2 in 60 specimens of pancreatic adenocarcinoma. The clinical significance of lipocalin‐2 was investigated in an analysis of correlations between lipocalin‐2 expression and matched clinical characteristics. A lipocalin‐2–expressing OV, ZD55‐lipocalin‐2, was constructed by deleting the adenoviral protein E1B55kD. The antitumor efficacy and mechanisms of the OV were investigated in pancreatic cancer cells with v‐Ki‐ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations in vitro and in vivo.RESULTS:Lipocalin‐2 expression was correlated with a good prognosis in patients with pancreatic adenocarcinoma. ZD55‐lipocalin‐2 dramatically inhibited the growth of pancreatic cancer in vitro and in vivo by inducing cytolysis and caspase‐dependent apoptosis.CONCLUSIONS:Higher lipocalin‐2 expression predicted a better prognosis in patients with pancreatic cancer. The results indicated that ZD55‐lipocalin‐2, which specifically expressed higher levels of lipocalin‐2 in tumor cells, may serve as a potent anticancer drug for pancreatic cancer therapy, especially for patients who have pancreatic adenocarcinoma with KRAS mutations. Cancer 2012. © 2012 American Cancer Society.
