Sodium selenite radiosensitizes hormone-refractory prostate cancer xenograft tumors but not intestinal crypt cells in vivo.
OBJECTIVE
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
Immunodeficient (SCID) mice with hormone-independent LAPC-4 (HI-LAPC-4) and PC-3 xenograft tumors (approximately 200 mm(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.
Tian
Junqiang
J
Department of Radiation Oncology, School of Medicine, Stanford University, Stanford, CA 94305-5152, USA.
Ning
Shouchen
S
Knox
Susan J
SJ
D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D003114:Colony-Forming Units Assay / Q000379:methods; D004334:Drug Administration Schedule; D004354:Drug Screening Assays, Antitumor; D004847:Epithelial Cells / Q000528:radiation effects*; D005260:Female; D005978:Glutathione / Q000032:analysis; D019803:Glutathione Disulfide / Q000032:analysis; D006801:Humans; D007274:Injections, Intraperitoneal; D007422:Intestines / Q000166:cytology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D016513:Mice, SCID; D009376:Neoplasms, Hormone-Dependent / Q000473:pathology / Q000532:radiotherapy; D011471:Prostatic Neoplasms / Q000737:chemistry / Q000473:pathology / Q000532:radiotherapy*; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D011879:Radiotherapy Dosage; D018038:Sodium Selenite / Q000627:therapeutic use*; D014183:Transplantation, Heterologous; D047368:Tumor Burden / Q000528:radiation effects
D011838:Radiation-Sensitizing Agents; D005978:Glutathione; D018038:Sodium Selenite; D019803:Glutathione Disulfide