Irradiation of Human Prostate Cancer Cells Increases Uptake of Antisense Oligodeoxynucleotide

Satoshi Anai, Bob D. Brown, Kogenta Nakamura, Steven Goodison, Yoshihiko Hirao, Charles J. Rosser

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Purpose: 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 and Materials: 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.

Original languageEnglish (US)
Pages (from-to)1161-1168
Number of pages8
JournalInternational Journal of Radiation Oncology Biology Physics
Volume68
Issue number4
DOIs
StatePublished - Jul 15 2007
Externally publishedYes

Fingerprint

Oligodeoxyribonucleotides
Prostatic Neoplasms
cancer
Heterografts
tumors
irradiation
dosage
Neoplasms
Ionizing Radiation
Software
cultured cells
ionizing radiation
Cell Line
computer programs
cells
oblimersen
Therapeutics

Keywords

  • Antisense
  • Cancer
  • Fluorescent
  • Oligodeoxynucleotide
  • Radiation

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Radiation

Cite this

Irradiation of Human Prostate Cancer Cells Increases Uptake of Antisense Oligodeoxynucleotide. / Anai, Satoshi; Brown, Bob D.; Nakamura, Kogenta; Goodison, Steven; Hirao, Yoshihiko; Rosser, Charles J.

In: International Journal of Radiation Oncology Biology Physics, Vol. 68, No. 4, 15.07.2007, p. 1161-1168.

Research output: Contribution to journalArticle

Anai, Satoshi ; Brown, Bob D. ; Nakamura, Kogenta ; Goodison, Steven ; Hirao, Yoshihiko ; Rosser, Charles J. / Irradiation of Human Prostate Cancer Cells Increases Uptake of Antisense Oligodeoxynucleotide. In: International Journal of Radiation Oncology Biology Physics. 2007 ; Vol. 68, No. 4. pp. 1161-1168.
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AB - Purpose: 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 and Materials: 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.

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