Vanilloids in pancreas cancer: potential for chemotherapy and pain management

Mark Hartel ¹, Fabio F Di Mola ¹, Federico Salvaggi ¹, Guiseppe Mascetta ¹, Moritz N Wente ¹, Klaus Felix ¹, Nathalia A Giese ¹, Ulf Hinz ¹, Pierluigi Di Sebastiano ¹, Markus W Buchler ¹ and Helmut Friess ^1*

¹ Department of Surgery, University of Heidelberg, Germany

^* To whom correspondence should be addressed. E-mail: helmut.friess{at}med.uni-heidelberg.de.

Accepted 6 September 2005

Abstract

Background:cess of chemotherapy and alleviation of pain are frequently less than optimal in pancreatic cancer patients, leading to increasing interest in new pharmacological substances like vanilloids. Our study addressed the question of whether vanilloids influence pancreas cancer cell growth, and if vanilloids could be used for pain treatment via the vanilloid 1 receptor (VR1) in pancreas cancer patients.

Methods: In vitro, the effect of resiniferatoxin (vanilloid analogon) on apoptosis and cell growth in pancreas cancer cells - either alone, combined with 5-FU, or combined with gemcitabine - was determined by annexin V staining, FACS analysis, and MTT assay, respectively. VR1 expression was evaluated on RNA and protein level by quantitative PCR and immunohistochemistry in human pancreatic cancer and chronic pancreatitis. Patient characteristics - especially pain levels - were registered in a prospective database and correlated to VR1 expression.

Results: Resiniferatoxin induces apoptosis by targeting mitochondrial respiration and decreases cell growth in pancreatic cancer cells without showing synergistic effects with 5-FU or gemcitabine. Expression of VR1 is significantly upregulated in human pancreas cancer and chronic pancreatitis. VR1 expression is related to the intensity of pain reported by cancer patients, but not to the intensity of pain reported by patients with chronic pancreatitis.

Conclusions: Resiniferatoxin-induced apoptosis in pancreas cancer cells indicates that vanilloids might be useful in the treatment of human pancreatic cancer. Furthermore, vanilloid might be a novel and effective treatment option for neurogenic pain in patients with pancreas cancer.

Keywords: apoptosis, pain treatment, pancreas cancer, vanilloid, vanilloid receptor 1

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