Suramin-induced decrease in prostate-specific antigen expression with no effect on tumor growth in the LNCaP model of...

Area of Science:

• Oncology
• Pharmacology
• Cancer Biology

Background:

• Suramin, an antitrypanosomal agent, shows potential in hormone-refractory prostate cancer.
• Serum prostate-specific antigen (PSA) reduction is a proposed efficacy endpoint.

Purpose of the Study:

• Evaluate suramin's antitumor effect in a mouse model of hormone-refractory prostate cancer.
• Determine if decreased PSA levels correlate with reduced tumor growth.
• Assess suramin's in vitro effects on cancer cell growth and PSA mRNA expression.

Main Methods:

• In vivo: C4-2 human prostate cancer cells xenografted in nude mice; suramin treatment administered intraperitoneally.
• In vitro: LNCaP and C4-2 cells exposed to suramin; cell growth assessed via crystal violet assay.
• PSA mRNA expression analyzed by northern blot; dihydrotestosterone (DHT) and hydrocortisone used as controls.

Main Results:

• In vivo, suramin did not significantly inhibit C4-2 tumor growth but decreased the ratio of PSA level to tumor volume.
• Suramin inhibited in vitro growth of androgen-dependent LNCaP cells, but not androgen-independent C4-2 cells.
• Suramin diminished PSA mRNA expression in both LNCaP and C4-2 cells in vitro.

Conclusions:

• Suramin inhibits androgen-dependent LNCaP cell growth but not androgen-independent C4-2 cell growth (in vitro and in vivo).
• Suramin decreases PSA mRNA expression and serum PSA levels in relevant models.
• Caution is advised when using PSA levels as an endpoint in suramin therapy for hormone-refractory prostate cancer.