Fasting cycles potentiate the efficacy of gemcitabine treatment in in vitro and in vivo pancreatic cancer models.

Abstract

BACKGROUND/AIMS:

Pancreatic cancer (PC) is ranked as the fourth leading cause of cancer-related deaths worldwide. Despite recent advances in treatment options, a modest impact on the outcome of the disease is observed so far. Short-term fasting cycles have been shown to potentiate the efficacy of chemotherapy against glioma. The aim of this study was to assess the effect of fasting cycles on the efficacy of gemcitabine, a standard treatment for PC patients, in vitro and in an in vivo pancreatic cancer mouse xenograft model.

MATERIALS AND METHODS:

BxPC-3, MiaPaca-2 and Panc-1 cells were cultured in standard and fasting mimicking culturing condition to evaluate the effects of gemcitabine. Pancreatic cancer xenograft mice were subjected to 24h starvation prior to gemcitabine injection to assess the tumor volume and weight as compared to mice fed ad libitum.

RESULTS:

Fasted pancreatic cancer cells showed increased levels of equilibrative nucleoside transporter (hENT1), the transporter of gemcitabine across the cell membrane, and decreased ribonucleotide reductase M1 (RRM1) levels as compared to those cultured in standard medium. Gemcitabine was more effective in inducing cell death on fasted cells as compared to controls. Consistently, xenograft pancreatic cancer mice subjected to fasting cycles prior to gemcitabine injection displayed a decrease of more than 40% in tumor growth.

CONCLUSIONS:

Fasting cycles enhance gemcitabine effect in vitro and in the in vivo PC xenograft mouse model. These results suggest that restrictive dietary interventions could enhance the efficacy of existing cancer treatments in pancreatic cancer patients.

• Authors: Martina D'Aronzo, Manlio Vinciguerra, Tommaso Mazza, Concetta Panebianco, Chiara Saracino, Stephen P Pereira, Paolo Graziano, Valerio Pazienza
• Journal: Oncotarget (Oncotarget) Vol. 6 Issue 21 Pg. 18545-57 (Jul 30 2015) ISSN: 1949-2553 [Electronic] United States
• PMID: 26176887 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antimetabolites, Antineoplastic
• Culture Media
• Equilibrative Nucleoside Transporter 1
• Proto-Oncogene Proteins c-bcl-2
• SLC29A1 protein, human
• Tumor Suppressor Proteins
• Deoxycytidine
• RRM1 protein, human
• Ribonucleoside Diphosphate Reductase
• TOR Serine-Threonine Kinases
• Gemcitabine

Topics

• Animals
• Antimetabolites, Antineoplastic (pharmacology)
• Cattle
• Cell Cycle (drug effects)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Survival (drug effects)
• Culture Media (chemistry, pharmacology)
• Deoxycytidine (analogs & derivatives, pharmacology)
• Equilibrative Nucleoside Transporter 1 (genetics, metabolism)
• Fasting
• Female
• Fetal Blood (chemistry)
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Immunoblotting
• Mice, Nude
• Microscopy, Fluorescence
• Pancreatic Neoplasms (drug therapy, genetics, metabolism)
• Proto-Oncogene Proteins c-bcl-2 (genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Ribonucleoside Diphosphate Reductase
• Signal Transduction (drug effects)
• TOR Serine-Threonine Kinases (metabolism)
• Tumor Suppressor Proteins (genetics, metabolism)
• Xenograft Model Antitumor Assays
• Gemcitabine