Abstract
The aim of this to study was to assess the biological consequences of cyclin D1 silencing in pancreatic cancer cells. A replication-defective lentivirus based small hairpin RNA (shRNA) system targeting cyclin D1 caused a marked reduction in cyclin D1 protein levels in ASPC-1 and BxPC3 pancreatic cancer cell lines in conjunction with decreased cell growth and invasiveness in vitro. Moreover, a single intratumoral injection of the recombinant lentivirus targeting cyclin D1 attenuated the growth of pre-existing tumors arising from two distinct cell lines. This attenuated growth correlated with decreased proliferation and angiogenesis, and attenuated VEGF expression. It is concluded that lentivirus-delivered shRNA targeting cyclin D1 suppresses the growth, invasiveness, tumorigenicity and pro-angiogenic potential of human pancreatic cancer cells, raising the possibility that intra-tumoral injections of viruses targeting cyclin D1 could provide a novel therapeutic approach in pancreatic ductal adenocarcinoma.
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