Delivery of miR-200c Mimic with Poly(amido amine) CXCR4 Antagonists for Combined Inhibition of Cholangiocarcinoma Cell Invasiveness

Ying Xie, Cody J. Wehrkamp, Jing Li, Yan Wang, Yazhe Wang, Justin L Mott, David Oupicky

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Cholangiocarcinoma is the second most common primary liver malignancy with extremely poor prognosis due to early invasion and widespread metastasis. The invasion and metastasis are regulated by multiple factors including CXCR4 chemokine receptor and multiple microRNAs. The goal of this study was to test the hypothesis that inhibition of CXCR4 combined with the action of miR-200c mimic will cooperatively enhance the inhibition of the invasion of human cholangiocarcinoma cells. The results show that CXCR4-inhibition polycation PCX can effectively deliver miR-200c mimic and that the combination treatment consisting of PCX and miR-200c results in cooperative antimigration activity, most likely by coupling the CXCR4 axis blockade with epithelial-to-mesenchymal transition inhibition in the cholangiocarcinoma cells. The ability of the combined PCX/miR-200c treatment to obstruct two migratory pathways represents a promising antimetastatic strategy in cholangiocarcinoma.

Original languageEnglish (US)
Pages (from-to)1073-1080
Number of pages8
JournalMolecular Pharmaceutics
Volume13
Issue number3
DOIs
StatePublished - Mar 7 2016

Fingerprint

Cholangiocarcinoma
Amines
CXCR4 Receptors
Neoplasm Metastasis
Epithelial-Mesenchymal Transition
Chemokine Receptors
MicroRNAs
tebufenozide
Liver
Neoplasms

Keywords

  • CXCR4
  • cholangiocarcinoma
  • microRNA
  • poly(amido amine)
  • polyplexes

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

Cite this

Delivery of miR-200c Mimic with Poly(amido amine) CXCR4 Antagonists for Combined Inhibition of Cholangiocarcinoma Cell Invasiveness. / Xie, Ying; Wehrkamp, Cody J.; Li, Jing; Wang, Yan; Wang, Yazhe; Mott, Justin L; Oupicky, David.

In: Molecular Pharmaceutics, Vol. 13, No. 3, 07.03.2016, p. 1073-1080.

Research output: Contribution to journalArticle

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AU - Li, Jing

AU - Wang, Yan

AU - Wang, Yazhe

AU - Mott, Justin L

AU - Oupicky, David

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AB - Cholangiocarcinoma is the second most common primary liver malignancy with extremely poor prognosis due to early invasion and widespread metastasis. The invasion and metastasis are regulated by multiple factors including CXCR4 chemokine receptor and multiple microRNAs. The goal of this study was to test the hypothesis that inhibition of CXCR4 combined with the action of miR-200c mimic will cooperatively enhance the inhibition of the invasion of human cholangiocarcinoma cells. The results show that CXCR4-inhibition polycation PCX can effectively deliver miR-200c mimic and that the combination treatment consisting of PCX and miR-200c results in cooperative antimigration activity, most likely by coupling the CXCR4 axis blockade with epithelial-to-mesenchymal transition inhibition in the cholangiocarcinoma cells. The ability of the combined PCX/miR-200c treatment to obstruct two migratory pathways represents a promising antimetastatic strategy in cholangiocarcinoma.

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