4.3 Article

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

期刊

PANCREAS
卷 45, 期 1, 页码 93-100

出版社

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/MPA.0000000000000427

关键词

molecular targeting; nestin; pancreatic cancer; metastasis; siRNA

资金

  1. Japan Society for the Promotion of Science [25462127]
  2. Cancer Research Institute of Kanazawa University
  3. Alumuni association of Kagawa University faculty of Medicine Sanjukai
  4. Grants-in-Aid for Scientific Research [25462127] Funding Source: KAKEN

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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.

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