Combination therapy of paclitaxel and cyclopamine polymer-drug conjugates to treat advanced prostate cancer

Ruinan Yang, Goutam Mondal, Di Wen, Ram I. Mahato

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Repeated treatments with chemotherapeutic agent(s) fail due to cancer stem cells (CSCs) and chemoresistance regulated by microRNAs (miRNA) whose expression alters owing to dysfunctional signaling pathways including Hedgehog (Hh) signaling. We previously demonstrated the combination of Hh inhibitor cyclopamine (CYP) and paclitaxel (PTX) effectively inhibit PTX-resistant cells and side population, a cell fraction rich in CSCs. In this study, we synthesized mPEG-b-PCC-g-PTX-g-DC (P-PTX) and mPEG-b-PCC-g-CYP-g-DC (P-CYP) polymer-drug conjugates, which they self-assembled into micelles. The combination of P-PTX and P-CYP alleviated PTX resistance and suppressed tumor colony formation. Further, combination therapy inhibited Hh signaling and up-regulated tumor suppressor miRNAs. We established orthotopic prostate tumor in nude mice and there was significant tumor growth inhibition in the group treated with the combination therapy of P-PTX and P-CYP compared with monotherapy. In conclusion, this combination therapy of P-PTX and P-CYP has the potential to treat chemoresistant prostate cancer.

Original languageEnglish (US)
Pages (from-to)391-401
Number of pages11
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume13
Issue number2
DOIs
StatePublished - Feb 1 2017

Keywords

  • Chemoresistance
  • Cyclopamine
  • Paclitaxel
  • Polymer-drug conjugate
  • Prostate cancer

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biomedical Engineering
  • Materials Science(all)
  • Pharmaceutical Science

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