Selenite treatment inhibits LAPC-4 tumor growth and prostate-specific antigen secretion in a xenograft model of human prostate cancer.

Abstract

PURPOSE:

Selenium compounds have known chemopreventive effects on prostate cancer. However selenite, an inorganic form of selenium, has not been extensively studied as a treatment option for prostate cancer. Our previous studies have demonstrated the inhibition of androgen receptor expression and androgen stimulated prostate-specific antigen (PSA) expression by selenite in human prostate cancer cell lines. In this study, we investigated the in vivo effects of selenite as a therapy to treat mice with established LAPC-4 tumors.

METHODS AND MATERIALS:

Male mice harboring androgen-dependent LAPC-4 xenograft tumors were treated with selenite (2 mg/kg intraperitoneally three times per week) or vehicle for 42 days. In addition, androgen-independent LAPC-4 xenograft tumors were generated in female mice over 4 to 6 months. Once established, androgen-independent LAPC-4 tumor fragments were passaged into female mice and were treated with selenite or vehicle for 42 days. Changes in tumor volume and serum PSA levels were assessed.

RESULTS:

Selenite significantly decreased androgen-dependent LAPC-4 tumor growth in male mice over 42 days (p < 0.001). Relative tumor volume was decreased by 41% in selenite-treated animals compared with vehicle-treated animals. The inhibition of LAPC-4 tumor growth corresponded to a marked decrease in serum PSA levels (p < 0.01). In the androgen-independent LAPC-4 tumors in female mice, selenite treatment decreased tumor volume by 58% after 42 days of treatment (p < 0.001).

CONCLUSIONS:

These results suggest that selenite may have potential as a novel therapeutic agent to treat both androgen-dependent and androgen-independent prostate cancer.

• Authors: Rumi S Bhattacharyya, Bryan Husbeck, David Feldman, Susan J Knox
• Journal: International journal of radiation oncology, biology, physics (Int J Radiat Oncol Biol Phys) Vol. 72 Issue 3 Pg. 935-40 (Nov 01 2008) ISSN: 1879-355X [Electronic] United States
• PMID: 18760546 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Androgens
• Antineoplastic Agents
• Biomarkers
• RNA, Messenger
• RNA, Neoplasm
• Prostate-Specific Antigen
• Sodium Selenite

Topics

• Androgens (physiology)
• Animals
• Antineoplastic Agents (pharmacology)
• Biomarkers (blood)
• Cell Division (drug effects)
• Cell Line, Tumor
• Female
• Humans
• Male
• Mice
• Prostate-Specific Antigen (blood)
• Prostatic Neoplasms (genetics, pathology)
• RNA, Messenger (genetics)
• RNA, Neoplasm (genetics)
• Reverse Transcriptase Polymerase Chain Reaction
• Sodium Selenite (pharmacology)
• Transplantation, Heterologous