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

Artur Plonowski, Andrew V Schally, Attila Nagy, Baodong Sun, Gabor Halmos

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)397-402
Number of pages6
JournalInternational Journal of Oncology
Volume20
Issue number2
StatePublished - Feb 1 2002
Externally publishedYes

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Somatostatin
Prostatic Neoplasms
Tumor Burden
Neoplasms
Nude Mice
Androgens
Therapeutics
Somatostatin Receptors
Messenger RNA
Injections
Poisons
AN 238
Carcinoma
Drug Therapy
Control Groups
Growth
AN 204

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Effective treatment of experimental DU-145 prostate cancers with targeted cytotoxic somatostatin analog AN-238. / Plonowski, Artur; Schally, Andrew V; Nagy, Attila; Sun, Baodong; Halmos, Gabor.

In: International Journal of Oncology, Vol. 20, No. 2, 01.02.2002, p. 397-402.

Research output: Contribution to journalArticle

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