Experimental study on the therapeutic effect and underlining mechanisms of positron in pancreatic cancer cells.

Ying Wang,Ming Li,Yaming Li,Dalong Zhang,Rao Diao,Brian Tung

doi:10.18632/oncotarget.18366

Abstract

The purpose of this study was to assess the potential therapeutic effect of positrons emitted by 18F-2-Deoxy-2-Fluoro-D-Glucose (18F-FDG) on pancreatic cancer cells and elucidate its underlying mechanisms. Pancreatic cancer cells were incubated with different radioactive concentrations of 18F-FDG and evaluated for anti-cancer properties and underlining mechanisms. In addition, three groups of tumor-bearing mice were treated with different doses of 18F-FDG weekly, the tumor growth rate was calculated, and the mice were imaged by positron emission tomography (PET) with 18F-FDG before and after treatment. The presence of apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) stain and immunohistochemistry analysis. All treated groups exhibited positron-inhibited proliferation and positron-induced apoptosis compared with the control group in vitro. Further, we noted that higher treatment dose correlated with a better treatment response. In vivo, the high dose administration of 18F-FDG reduced tumor growth and prolonged the survival of treated mice compared with the control group with no change in the behavior or normal tissues of the mice. Immunohistochemical analysis and TUNEL stain showed more apoptotic cells than that in control group. The results demonstrated that positron radiation inhibited the proliferation and induced apoptosis of pancreatic cancer cells in vitro and in vivo, via an endogenous mitochondria-mediated signaling pathway.

Highlights

Pancreatic cancer is the tenth most common malignant tumor worldwide with its incidence rising dramatically in recent years
The 3H-TdR DNA synthesis results showed that with the increase of 18F-FDG radioactive concentration, the counts per minute (CPM) of cells and incorporation rate of 3H-TdR gradually decreased compared with the control group (Figure 1D), which indicated that positron radiation could inhibit the DNA synthesis of pancreatic cancer cells
The results of 3 pancreatic cancer cells treated with 18F-FDG demonstrated similar efficacy in inhibiting proliferation and inducing apoptosis, so we further investigated the underlying mechanisms of apoptosis induced by positron

Summary

Introduction

Pancreatic cancer is the tenth most common malignant tumor worldwide with its incidence rising dramatically in recent years. It is highly lethal, and the prognosis remains poor. 18F-FDG-6-phosphate cannot be readily dephosphorylated, so it remains trapped in cells [6,7]. A number of studies [11,12,13,14,15] have shown the feasibility of using positron emitted by 18F-FDG to treat high glycolytic tumors, such as lung, breast, and colon cancer, by inducing apoptosis or necrosis and inhibiting tumor growth rate, www.impactjournals.com/oncotarget definitively. The high glycolytic rate of pancreatic cancer cells reflects in the increased uptake and accumulation of 18F-FDG, making 18F-FDG a candidate agent for positron therapy against pancreatic cancers

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