Systemic Administration of Small Interfering RNA Targeting Human Nestin Inhibits Pancreatic Cancer Cell Proliferation and Metastasis

OBJECTIVES: Nestin, a progenitor/stem cell marker, is expressed in human pancreatic cancer, where its expression correlates positively with invasiveness and metastasis. Here, we investigated the inhibition of nestin expression and the regulation of nestin expression. METHODS: We analyzed the effects of small interfering RNA (siRNA) targeting nestin using pancreatic cancer cell lines. RESULTS: Nestin siRNA inhibited the growth, migration, invasion, and sphere-forming ability of the pancreatic cancer cell lines. Pancreatic cancer cells cotreated with gemcitabine and nestin siRNA exhibited lower cell viability than cells treated with a control siRNA, gemcitabine alone, or nestin siRNA alone. Cells derived from the metastatic nodules of mice showed higher nestin expression than the parental cells, and nestin expression in pancreatic cancer cells was regulated by methylation of the nestin gene. In an orthotopic implantation model using mice, administration of nestin siRNA significantly decreased primary and metastatic tumor formation by human pancreatic cancer cells compared to tumor formation in control siRNA-treated mice. CONCLUSIONS: Nestin plays a key role in pancreatic cancer cell metastasis and stemness and that administration of nestin siRNA may offer a novel therapeutic strategy for pancreatic cancer.