Cyclopamine increases the cytotoxic effects of paclitaxel and radiation but not cisplatin and gemcitabine in Hedgehog expressing pancreatic cancer cells

Cancer Chemother Pharmacol. 2006 Dec;58(6):765-70. doi: 10.1007/s00280-006-0227-4. Epub 2006 Mar 22.


Introduction: The hedgehog signaling pathway (Hh) is frequently over expressed in pancreatic adenocarcinomas. We studied the potential cytotoxic interactions between cyclopamine, a Hh pathway inhibitor and paclitaxel, cisplatin, gemcitabine and ionizing radiation (IR).

Methods: In vitro clonogenic survival analysis was performed with cyclopamine alone or cyclopamine in combination with paclitaxel, gemcitabine, cisplatin and IR in Hh expressing human pancreatic tumor cells and Hh non-expressing colon cancer cells. Relative cytotoxicity was assessed in combination treatment compared with exposure to single agents. Assays of apoptosis (annexin V) were performed in the presence of cyclopamine, chemotherapeutic agents, and IR.

Results: We report that cyclopamine increased the cytotoxic effects of paclitaxel and IR in Hh expressing pancreatic carcinoma cells. These effects were not observed in Hh non-expressing cells. Cyclopamine did not significantly increase killing by cisplatin or gemcitabine in Hh expressing pancreatic cancer cells.

Conclusions: These data suggest strategies to combine Hh inhibitors with radiotherapy and chemotherapeutic agents, specifically paclitaxel and related compounds in the treatment of pancreatic cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Apoptosis / radiation effects
  • Cell Cycle / drug effects
  • Cell Cycle / radiation effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cell Survival / radiation effects
  • Cisplatin / pharmacology*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / physiopathology
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / pharmacology
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Gemcitabine
  • HCT116 Cells
  • Hedgehog Proteins / antagonists & inhibitors
  • Hedgehog Proteins / biosynthesis*
  • Humans
  • Paclitaxel / pharmacology*
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology
  • Pancreatic Neoplasms / physiopathology
  • Radiation, Ionizing
  • Time Factors
  • Veratrum Alkaloids / pharmacology*


  • Antineoplastic Agents
  • Hedgehog Proteins
  • Veratrum Alkaloids
  • Deoxycytidine
  • Paclitaxel
  • Cisplatin
  • cyclopamine
  • Gemcitabine