Sodium Selenite Radiosensitizes Hormone-Refractory Prostate Cancer Xenograft Tumors but Not Intestinal Crypt Cells In Vivo
- Department of Radiation Oncology, School of Medicine, Stanford University, Stanford, CA (United States)
Purpose: We have previously shown that sodium selenite (SSE) increases radiation-induced cell killing of human prostate carcinoma cells in vitro. In this study we further evaluated the in vivo radiosensitizing effect of SSE in prostate cancer xenograft tumors and normal radiosensitive intestinal crypt cells. Methods and Materials: Immunodeficient (SCID) mice with hormone-independent LAPC-4 (HI-LAPC-4) and PC-3 xenograft tumors (approximately 200 mm{sup 3}) were divided into four groups: control (untreated), radiation therapy (XRT, local irradiation), SSE (2 mg/kg, intraperitoneally, 3 times/week), and XRT plus SSE. The XRT was given at the beginning of the regimen as a single dose of 5 Gy for HI-LAPC-4 tumors and a single dose of 7 Gy followed by a fractional dose of 3 Gy/d for 5 days for PC-3 tumors. The tumor volume was measured 3 times per week. The radiosensitizing effect of SSE on normal intestinal epithelial cells was assessed by use of a crypt cell microcolony assay. Results: In the efficacy study, SSE alone significantly inhibited the tumor growth in HI-LAPC-4 tumors but not PC-3 tumors. Sodium selenite significantly enhanced the XRT-induced tumor growth inhibition in both HI-LAPC-4 and PC-3 tumors. In the toxicity study, SSE did not affect the intestinal crypt cell survival either alone or in combination with XRT. Conclusions: Sodium selenite significantly enhances the effect of radiation on well-established hormone-independent prostate tumors and does not sensitize the intestinal epithelial cells to radiation. These results suggest that SSE may increase the therapeutic index of XRT for the treatment of prostate cancer.
- OSTI ID:
- 21451151
- Journal Information:
- International Journal of Radiation Oncology, Biology and Physics, Vol. 78, Issue 1; Other Information: DOI: 10.1016/j.ijrobp.2010.03.006; PII: S0360-3016(10)00409-8; Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0360-3016
- Country of Publication:
- United States
- Language:
- English
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62 RADIOLOGY AND NUCLEAR MEDICINE
CARCINOMAS
CELL KILLING
CRYPT CELLS
HORMONES
IN VIVO
MICE
PROSTATE
RADIOSENSITIZERS
RADIOTHERAPY
SELENITES
SODIUM COMPOUNDS
ALKALI METAL COMPOUNDS
ANIMAL CELLS
ANIMALS
BODY
DISEASES
DRUGS
GLANDS
MALE GENITALS
MAMMALS
MEDICINE
NEOPLASMS
NUCLEAR MEDICINE
ORGANS
OXYGEN COMPOUNDS
RADIOLOGY
RESPONSE MODIFYING FACTORS
RODENTS
SELENIUM COMPOUNDS
SOMATIC CELLS
THERAPY
VERTEBRATES