Tumor-specific Apoptotic Gene Targeting Overcomes Radiation Resistance in Esophageal Adenocarcinoma

Overview

Journal Int J Radiat Oncol Biol Phys

Specialties Oncology
Radiology

Date 2006 Apr 4

PMID 16580499

Citations 3

Authors

Joe Y Chang

Xiaochun Zhang

Ritsuko Komaki

Rex Cheung

Bingliang Fang

Affiliations

Soon will be listed here.

Abstract

Purpose: To overcome radiation resistance in esophageal adenocarcinoma by tumor-specific apoptotic gene targeting using tumor necrosis factor-related apoptosis-inducing ligand (TRAIL).

Methods And Materials: Adenoviral vector Ad/TRAIL-F/RGD with a tumor-specific human telomerase reverse transcription promoter was used to transfer TRAIL gene to human esophageal adenocarcinoma and normal human lung fibroblastic cells (NHLF). Activation of apoptosis was analyzed by Western blot, fluorescent activated cell sorting, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate labeling (TUNEL) assay. A human esophageal adenocarcinoma mouse model was treated with intratumoral injections of Ad/TRAIL-F/RGD plus local radiotherapy.

Results: The combination of Ad/TRAIL-F/RGD and radiotherapy increased the cell-killing effect in all esophageal adenocarcinoma cell lines but not in NHLF cells. This combination also significantly reduced clonogenic formation (p < 0.05) and increased sub-G1 deoxyribonucleic acid accumulation in cancer cells (p < 0.05). Activation of apoptosis by Ad/TRAIL-F/RGD plus radiotherapy was demonstrated by activation of caspase-9, caspase-8, and caspase-3 and cleaved poly (adenosine diphosphate-ribose) polymerase in vitro and TUNEL assay in vivo. Combined Ad/TRAIL-F/RGD and radiotherapy dramatically inhibited tumor growth and prolonged mean survival in the esophageal adenocarcinoma model to 31.6 days from 16.7 days for radiotherapy alone and 21.5 days for Ad/TRAIL-F/RGD alone (p < 0.05).

Conclusions: The combination of tumor-specific TRAIL gene targeting and radiotherapy enhances the effect of suppressing esophageal adenocarcinoma growth and prolonging survival.

Citing Articles

Therapy-resistant cancer stem cells have differing sensitivity to photon versus proton beam radiation.

Zhang X, Lin S, Fang B, Gillin M, Mohan R, Chang J J Thorac Oncol. 2014; 8(12):1484-91.

PMID: 24389430 PMC: 3882687. DOI: 10.1097/JTO.0b013e3182a5fdcb.

Coxsackie-adenovirus receptor as a novel marker of stem cells in treatment-resistant non-small cell lung cancer.

Zhang X, Fang B, Mohan R, Chang J Radiother Oncol. 2012; 105(2):250-7.

PMID: 23022172 PMC: 3845342. DOI: 10.1016/j.radonc.2012.09.002.

Treatment of radioresistant stem-like esophageal cancer cells by an apoptotic gene-armed, telomerase-specific oncolytic adenovirus.

Zhang X, Komaki R, Wang L, Fang B, Chang J Clin Cancer Res. 2008; 14(9):2813-23.

PMID: 18451249 PMC: 2387204. DOI: 10.1158/1078-0432.CCR-07-1528.

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