Irradiation of human prostate cancer cells increases uptake of antisense oligodeoxynucleotide.
OBJECTIVE
To investigate whether irradiation before antisense Bcl-2 oligodeoxynucleotide (ODN) administration enhances tissue uptake, and whether periodic dosing enhances cellular uptake of fluorescently labeled ODN relative to constant dosing.


METHODS
PC-3-Bcl-2 cells (prostate cancer cell line engineered to overexpress Bcl-2) were subjected to increasing doses of irradiation (0-10 Gy) with or without increasing concentrations of fluorescently labeled antisense Bcl-2 ODN (G4243). The fluorescent signal intensity was quantified as the total grain area with commercial software. In addition, PC-3-Bcl-2 subcutaneous xenograft tumors were treated with or without irradiation in combination with various dosing schemas of G4243. The uptake of fluorescent G4243 in tumors was quantitated.


RESULTS
The uptake of G4243 was increased in prostate cancer cells exposed to low doses of irradiation both in vitro and in vivo. Irradiation before G4243 treatment resulted in increased fluorescent signal intensity in xenograft tumors compared with those irradiated after G4243 treatment. A single weekly dose of G4243 produced higher G4243 uptake in xenograft tumors than daily dosing, even when the total dose administered per week was held constant.


CONCLUSIONS
These findings suggest that ionizing radiation increases the uptake of therapeutic ODN in target tissues and, thus, has potential to increase the efficacy of ODN in clinical applications.
Anai
Satoshi
S
Prostate Cancer Translational Working Group, University of Florida, Jacksonville, FL, USA.
Brown
Bob D
BD
Nakamura
Kogenta
K
Goodison
Steve
S
Hirao
Yoshihiko
Y
Rosser
Charles J
CJ
D000818:Animals; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy / Q000379:methods; D005453:Fluorescence; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy*; D011829:Radiation Dosage; D013873:Thionucleotides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014183:Transplantation, Heterologous
D016376:Oligonucleotides, Antisense; D013873:Thionucleotides; C408162:oblimersen