Effective treatment of experimental DU-145 prostate cancers with targeted cytotoxic somatostatin analog AN-238.

Abstract

We evaluated the effectiveness of targeted cytotoxic analog of somatostatin (SST) AN-238, consisting of 2-pyrrolinodoxorubicin (AN-201) linked covalently to SST octapeptide carrier RC-121 in DU-145 human androgen-independent prostate cancers xenografted into nude mice. We also investigated the expression of mRNAs for SST receptor subtypes 2A and 5 (sst2A and sst5) in DU-145 tumors. After 8 weeks of treatment, AN-238 practically arrested the proliferation of DU-145 cancers. The tumor volume in nude mice that received 4 injections of AN-238 at the dose of 150 nmol/kg was 63.4+/-6.7 mm3, nearly 4 times smaller than that in controls which measured 249.1+/-36.3 mm3 (p<0.001). Treatment with AN-238 lowered tumor weight by 68% (p<0.01) compared with the control group and extended the tumor volume doubling time to 184.1+/-69.4 days, versus 32.1+/-6.6 days in controls (p<0.05). No toxicity-related deaths occurred during treatment with AN-238. Cytotoxic radical AN-201 administered alone or in an unconjugated mixture with carrier RC-121 inhibited the growth of DU-145 tumors only after the third and fourth injection and was toxic. The expression of mRNA for sst2A and sst5 was detected in all specimens of control DU-145 tumors and in tumors treated with AN-238. The present study demonstrates the high efficacy of SST-receptor-targeted chemotherapy in a model of human androgen-independent prostatic carcinoma.

• Authors: Artur Plonowski, Andrew V Schally, Attila Nagy, Baodong Sun, Gabor Halmos
• Journal: International journal of oncology (Int J Oncol) Vol. 20 Issue 2 Pg. 397-402 (Feb 2002) ISSN: 1019-6439 [Print] Greece
• PMID: 11788908 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• AN 238
• Antibiotics, Antineoplastic
• Cytotoxins
• Pyrroles
• RNA, Messenger
• RNA, Neoplasm
• AN 204
• Doxorubicin
• RC 121
• Octreotide

Topics

• Animals
• Antibiotics, Antineoplastic (pharmacology, therapeutic use)
• Cell Division (drug effects)
• Cytotoxins (pharmacology, therapeutic use)
• Doxorubicin (analogs & derivatives, pharmacology, therapeutic use)
• Gene Expression Regulation, Neoplastic
• Humans
• Male
• Mice
• Mice, Nude
• Neoplasm Transplantation
• Neoplasms, Experimental (drug therapy, pathology)
• Octreotide (analogs & derivatives, pharmacology)
• Prostatic Neoplasms (drug therapy, pathology)
• Pyrroles (pharmacology, therapeutic use)
• RNA, Messenger (genetics, metabolism)
• RNA, Neoplasm (genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Treatment Outcome
• Tumor Cells, Cultured