Cyclopamine-loaded core-cross-linked polymeric micelles enhance radiation response in pancreatic cancer and pancreatic stellate cells.

Journal Article (Journal Article)

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers. Cyclopamine (CPA), a potent inhibitor for sonic hedgehog pathway (SHH), shows great promises in PDAC treatment, including the disruption of tumor-associated stroma, and enhancement of radiation therapy. However, CPA is insoluble in water and therefore requires a nanometric delivery platform to achieve satisfactory performance. We herein encapsulated CPA in a core-cross-linked polymeric micelle system (M-CPA). M-CPA was combined with Cs-137 radiation and evaluated in vitro in PDAC cell lines and a human pancreatic stellate cell line. The results showed that M-CPA had higher cytotoxicity than CPA, abolished Gli-1 expression (a key component of SHH), and enhanced the radiation therapy of Cs-137. M-CPA radiosensitization correlated with its ability to disrupt the repair of radiation-induced DNA damage. These findings indicate that the combination therapy of M-CPA and radiation is an effective strategy to simultaneously treat pancreatic tumors and tumor-associated stroma.

Full Text

Duke Authors

Cited Authors

  • Zhao, J; Wu, C; Abbruzzese, J; Hwang, RF; Li, C

Published Date

  • June 1, 2015

Published In

Volume / Issue

  • 12 / 6

Start / End Page

  • 2093 - 2100

PubMed ID

  • 25936695

Pubmed Central ID

  • PMC5055750

Electronic International Standard Serial Number (EISSN)

  • 1543-8392

Digital Object Identifier (DOI)

  • 10.1021/mp500875f


  • eng

Conference Location

  • United States