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Targeting of cytotoxic somatostatin analog AN-238 to somatostatin receptor subtypes 5 and/or 3 in experimental pancreatic cancers.

Publication ,  Journal Article
Szepeshazi, K; Schally, AV; Halmos, G; Sun, B; Hebert, F; Csernus, B; Nagy, A
Published in: Clin Cancer Res
September 2001

PURPOSE: The expression of somatostatin receptors (SSTRs) allows the localization and treatment of some tumors with radiolabeled SST analogues. We investigated whether SSTRs on human pancreatic cancer lines xenografted into nude mice can be used for targeting of cytotoxic somatostatin analogue AN-238, consisting of 2-pyrrolinodoxorubicin (AN-201) linked to octapeptide carrier RC-121. EXPERIMENTAL DESIGN: AN-238 and AN-201 were administered i.v. to nude mice bearing SW-1990 pancreatic cancers. Tumor growth reduction and survival were analyzed, and cell proliferation and apoptosis were determined with histological methods. The effects of repeated administration of AN-238 and AN-201 were also evaluated on xenografted Panc-1, MiaPaCa-2, CFPAC-1, Capan-1, and Capan-2 pancreatic cancers. The expression of mRNA for SSTR subtypes 2A, 3, and 5 in tumors was analyzed by reverse transcription-PCR, and binding assays were performed. RESULTS: All of the cancer models except MiaPaCa-2 displayed functional receptors for SST. SW-1990 expressed mRNA for SSTR subtypes 3 and 5, whereas various patterns of subtypes 2A, 3, and 5 were found in other pancreatic cancers. Repeated administration of AN-238 at 150 nmol/kg significantly inhibited growth of SW-1990 cancers (93% after 45 days; P = 0.016) and other tumors but not MiaPaCa-2. AN-201 was toxic and less effective. The efficacy of AN-238 was consistent with SSTR expression. CONCLUSIONS: Growth of experimental human pancreatic cancers that express SSTRs can be inhibited by cytotoxic somatostatin analogue AN-238.

Duke Scholars

Published In

Clin Cancer Res

ISSN

1078-0432

Publication Date

September 2001

Volume

7

Issue

9

Start / End Page

2854 / 2861

Location

United States

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • Tumor Cells, Cultured
  • Time Factors
  • Survival Analysis
  • Receptors, Somatostatin
  • RNA, Messenger
  • Pyrroles
  • Pancreatic Neoplasms
  • Oncology & Carcinogenesis
  • Neoplasms, Experimental
 

Citation

APA
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ICMJE
MLA
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Szepeshazi, K., Schally, A. V., Halmos, G., Sun, B., Hebert, F., Csernus, B., & Nagy, A. (2001). Targeting of cytotoxic somatostatin analog AN-238 to somatostatin receptor subtypes 5 and/or 3 in experimental pancreatic cancers. Clin Cancer Res, 7(9), 2854–2861.
Szepeshazi, K., A. V. Schally, G. Halmos, B. Sun, F. Hebert, B. Csernus, and A. Nagy. “Targeting of cytotoxic somatostatin analog AN-238 to somatostatin receptor subtypes 5 and/or 3 in experimental pancreatic cancers.Clin Cancer Res 7, no. 9 (September 2001): 2854–61.
Szepeshazi K, Schally AV, Halmos G, Sun B, Hebert F, Csernus B, et al. Targeting of cytotoxic somatostatin analog AN-238 to somatostatin receptor subtypes 5 and/or 3 in experimental pancreatic cancers. Clin Cancer Res. 2001 Sep;7(9):2854–61.
Szepeshazi, K., et al. “Targeting of cytotoxic somatostatin analog AN-238 to somatostatin receptor subtypes 5 and/or 3 in experimental pancreatic cancers.Clin Cancer Res, vol. 7, no. 9, Sept. 2001, pp. 2854–61.
Szepeshazi K, Schally AV, Halmos G, Sun B, Hebert F, Csernus B, Nagy A. Targeting of cytotoxic somatostatin analog AN-238 to somatostatin receptor subtypes 5 and/or 3 in experimental pancreatic cancers. Clin Cancer Res. 2001 Sep;7(9):2854–2861.

Published In

Clin Cancer Res

ISSN

1078-0432

Publication Date

September 2001

Volume

7

Issue

9

Start / End Page

2854 / 2861

Location

United States

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • Tumor Cells, Cultured
  • Time Factors
  • Survival Analysis
  • Receptors, Somatostatin
  • RNA, Messenger
  • Pyrroles
  • Pancreatic Neoplasms
  • Oncology & Carcinogenesis
  • Neoplasms, Experimental