Epothilone B Confers Radiation Dose Enhancement in DAB2IP Gene Knock-Down Radioresistant Prostate Cancer Cells

Journal Article · Sun Nov 14 23:00:00 EST 2010 · International Journal of Radiation Oncology, Biology and Physics

DOI:https://doi.org/10.1016/j.ijrobp.2010.06.019· OSTI ID:21451165

Zhaolu, Kong ^[1]; Raghavan, Pavithra ^[1]; Daxing, Xie ^[2]; Boike, Thomas ^[1]; Burma, Sandeep; Chen, David ^[1]; Chakraborty, Arup ^[3]; Hsieh, Jer-Tsong ^[2]; Saha, Debabrata ^[1]

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1. Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX (United States)
2. Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX (United States)
3. College of Pharmacy, University of Southern Nevada, Henderson, NV (United States)

Purpose: In metastatic prostate cancer, DOC-2/DAB2 interactive protein (DAB2IP) is often downregulated and has been reported as a possible prognostic marker to predict the risk of aggressive prostate cancer (PCa). Our preliminary results show that DAB2IP-deficient PCa cells are radioresistant. In this study, we investigated the anticancer drug Epothilone B (EpoB) for the modulation of radiosensitivity in DAB2IP-deficient human PCa cells. Methods and Materials: We used a stable DAB2IP-knock down human PCa cell line, PC3 shDAB2IP, treated with EpoB, ionizing radiation (IR), or the combined treatment of EpoB and IR. The modulation of radiosensitivity was determined by surviving fraction, cell cycle distribution, apoptosis, and DNA double-strand break (DSB) repair. For in vivo studies, the PC3shDAB2IP xenograft model was used in athymic nude mice. Results: Treatment with EpoB at IC{sub 50} dose (33.3 nM) increased cellular radiosensitivity in the DAB2IP-deficient cell line with a dose enhancement ratio of 2.36. EpoB delayed the DSB repair kinetics after IR and augmented the induction of apoptosis in irradiated cells after G{sub 2}/M arrest. Combined treatment of EpoB and radiation enhanced tumor growth delay with an enhancement factor of 1.2. Conclusions: We have demonstrated a significant radiation dose enhancement using EpoB in DAB2IP-deficient prostate cancer cells. This radiosensitization can be attributed to delayed DSB repair, prolonged G{sub 2} block, and increased apoptosis in cells entering the cell cycle after G{sub 2}/M arrest.

• OSTI ID: 21451165
• Journal Information: International Journal of Radiation Oncology, Biology and Physics, Journal Name: International Journal of Radiation Oncology, Biology and Physics Journal Issue: 4 Vol. 78; ISSN IOBPD3; ISSN 0360-3016
• Country of Publication: United States
• Language: English

Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANTINEOPLASTIC DRUGS
APOPTOSIS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
BODY
CELL CYCLE
DISEASES
DNA DAMAGES
DNA REPAIR
DOSES
DRUGS
GENES
GLANDS
IN VIVO
MALE GENITALS
MODULATION
NEOPLASMS
ORGANIC COMPOUNDS
ORGANS
PROSTATE
PROTEINS
RADIATION DOSES
RADIOSENSITIVITY
REPAIR
SENSITIVITY
STRAND BREAKS
TUMOR CELLS