TY - JOUR
T1 - Inhibition of in vivo proliferation of MDA-PCa-2b human prostate cancer by a targeted cytotoxic analog of luteinizing hormone-releasing hormone AN-207
AU - Plonowski, Artur
AU - Schally, Andrew V.
AU - Nagy, Attila
AU - Groot, Kate
AU - Krupa, Magdalena
AU - Navone, Nora M.
AU - Logothetis, Christopher
N1 - Funding Information:
We thank Mrs Elena Glotser for expert technical assistance. This work was supported by the Medical Research Service of the Veterans Affairs Department, a grant from Zentaris AG (Frankfurt am Main, Germany), and by an award from CaP CURE Foundation to Tulane University School of Medicine (all to A.V.S.).
PY - 2002/2/8
Y1 - 2002/2/8
N2 - 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-Lys6]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.
AB - 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-Lys6]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.
KW - Luteinizing hormone-releasing hormone
KW - Luteinizing hormone-releasing hormone receptors
KW - Prostate cancer
KW - Targeted chemotherapy
UR - http://www.scopus.com/inward/record.url?scp=0037039710&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037039710&partnerID=8YFLogxK
U2 - 10.1016/S0304-3835(01)00734-0
DO - 10.1016/S0304-3835(01)00734-0
M3 - Article
C2 - 11790454
AN - SCOPUS:0037039710
SN - 0304-3835
VL - 176
SP - 57
EP - 63
JO - Cancer Letters
JF - Cancer Letters
IS - 1
ER -