PANCREATIC CANCER

Vanilloids in pancreatic cancer: potential for chemotherapy and pain management

M Hartel, F F di Mola, F Selvaggi, G Mascetta, M N Wente, K Felix, N A Giese, U Hinz, P Di Sebastiano, M W Büchler, H Friess

Department of General Surgery, University of Heidelberg, Heidelberg, Germany

Correspondence to:
Dr H Friess
Department of General Surgery, Im Neuenheimer Feld 110, D-69120 Heidelberg, Germany; helmut.friess{at}med.uni-heidelberg.de

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

Methods: In vitro, the effect of resiniferatoxin (vanilloid analogue) on apoptosis and cell growth in pancreatic cancer cells—either alone, combined with 5-fluorouracil (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 polymerase chain reaction and immunohistochemistry in human pancreatic cancer and chronic pancreatitis. Patient characteristics—especially pain levels—were registered in a prospective database and correlated with VR1 expression.

Results: Resiniferatoxin induced apoptosis by targeting mitochondrial respiration and decreased cell growth in pancreatic cancer cells without showing synergistic effects with 5-FU or gemcitabine. Expression of VR1 was significantly upregulated in human pancreatic cancer and chronic pancreatitis. VR1 expression was 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 pancreatic cancer cells indicates that vanilloids may 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 pancreatic cancer.

Abbreviations: VR1, vanilloid 1 receptor; FACS, fluorescence activated cell sorter; 5-FU, 5-fluorouracil; VAS, visual analogue scale; HRP, horseradish peroxidase; PCR, polymerase chain reaction; DCFH-DA, 2',7'-dichlorodihydroflourescein diacetate; DCF, 2',7'-dichlorofluorescein

Keywords: vanilloid; vanilloid 1 receptor; apoptosis; pancreatic cancer; pain treatment

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