Inhibition of in vivo proliferation of MDA-PCa-2b human prostate cancer by a targeted cytotoxic analog of luteinizing hormone-releasing hormone AN-207.

Abstract

The efficacy of therapy with targeted cytotoxic luteinizing hormone-releasing hormone (LHRH) analog AN-207 consisting of superactive doxorubicin derivative AN-201 linked to carrier [D-Lys(6)]LH-RH was evaluated in vivo in nude mice bearing xenografts of MDA-PCa-2b prostate cancer line. AN-207 was administered intravenously (i.v.) at 200 nmol/kg on day 1 and at 150 nmol/kg on day 14. After 4 weeks of treatment with AN-207, tumor growth was inhibited as shown by a 63% (P<0.01) decrease in tumor volume and a 55% (P<0.05) reduction in tumor weight, compared with controls. None of the animals died after administration of AN-207 at the total dose of 350 nmol/kg, and at the end of the experiment the body weights of mice given AN-207 did not differ significantly from controls. A single injection of cytotoxic radical AN-201 at 200 nmol/kg resulted in 43% mortality. In the surviving mice, AN-201 caused a 50% inhibition in tumor volume and a 27% reduction in tumor weight, which were non-significant, as compared to the controls. After 4 weeks, serum prostate-specific antigen concentrations in mice treated with AN-207 were 65% lower than those in controls (P<0.05), while in animals given AN-201 the reduction in serum prostate-specific antigen was only 40% (NS). The expression of mRNA for LHRH receptors was detected by reverse transcriptase polymerase chain reaction (RT-PCR) in MDA-PCa-2b tumors. The present study indicates that chemotherapy targeted to LHRH receptors on tumors inhibits growth of MDA-PCa-2B prostate cancers representative of human carcinoma disseminated to the bone and progressing despite androgen withdrawal.

• Authors: Artur Plonowski, Andrew V Schally, Attila Nagy, Kate Groot, Magdalena Krupa, Nora M Navone, Christopher Logothetis
• Journal: Cancer letters (Cancer Lett) Vol. 176 Issue 1 Pg. 57-63 (Feb 08 2002) ISSN: 0304-3835 [Print] Ireland
• PMID: 11790454 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Antineoplastic Agents
• RNA, Messenger
• AN 207
• Gonadotropin-Releasing Hormone
• Doxorubicin
• Luteinizing Hormone

Topics

• Animals
• Antineoplastic Agents (therapeutic use)
• Cell Division
• Dose-Response Relationship, Drug
• Doxorubicin (analogs & derivatives, therapeutic use)
• Gonadotropin-Releasing Hormone (analogs & derivatives, therapeutic use)
• Humans
• Luteinizing Hormone (analogs & derivatives)
• Male
• Mice
• Mice, Nude
• Prostatic Neoplasms (drug therapy, pathology)
• RNA, Messenger (metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Time Factors
• Tumor Cells, Cultured