Targeted cytotoxic analog of luteinizing hormone-releasing hormone AN-207 inhibits the growth of PC-82 human prostate cancer in nude mice

✍ Scribed by Kopp�n, Miklos; Nagy, Attila; Schally, Andrew V.; Plonowski, Artur; Halmos, G�bor; Arencibia, Jos� M.; Groot, Kate

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 238 KB
• Volume: 38
• Category: Article
• ISSN: 0270-4137
• DOI: 10.1002/(sici)1097-0045(19990201)38:2<151::aid-pros9>3.0.co;2-#

✦ Synopsis

Background:

Receptors for luteinizing hormone-releasing hormone (lh-rh) found in prostate cancers might be used for targeting of chemotherapeutic agents. doxorubicin derivative 2-pyrrolinodoxorubicin (an-201) can be linked to carrier analog [d-lys6]lh-rh to form the targeted cytotoxic analog of lh-rh, an-207.

Methods:

We evaluated the effects of an-207 and its components on the growth of lh-rh receptor-positive human prostate cancer pc-82 xenografted into nude mice. analog an-207, radical an-201, carrier [d-lys6]lh-rh, or a mixture of [d-lys6]lh-rh and an-201 were injected intravenously once at doses of 200 nmol/kg. tumor growth, body weight, total wbc counts, and serum prostate-specific antigen (psa) were determined. receptors for lh-rh on pc-82 tumors were evaluated, and the expression of mrna for lh-rh receptors was assessed by rt-pcr.

Results:

Eight weeks after administration of cytotoxic analog an-207, there was a 67.8% reduction in tumor volume (p < 0.01), 70.7% decrease in tumor burden (p < 0.01), and 36.5% decrease in serum psa levels (p < 0.01) as compared with controls. only one of 8 animals treated with an-207 died. cytotoxic radical an-201 caused a 34.2% (not significant, ns) reduction in tumor volume with no change in serum psa, and killed 3 of 8 mice due to toxicity. carrier [d-lys6]lh-rh and the unconjugated mixture of [d-lys6]lh-rh and an-201 had no effect on tumor growth. lh-rh receptors as well as the expression of their mrna were found in pc-82 tumors.