Abstract
Objectives: Targeting anticancer agents to receptors for peptide hormones such as bombesin/gastrin-releasing peptide (GRP) on tumor cells increases the efficacy and lowers the toxicity of cancer therapy. We studied the expression of bombesin/GRP receptors in 6 experimental pancreatic cancers and evaluated tumor inhibition in vivo produced by targeted chemotherapy with the cytotoxic bombesin analog AN-215. Methods: Nude mice with xenografts of Pane-1, CFPAC-1, Capan-1, Capan-2, MiaPaCa-2, and SW-1990 human ductal pancreatic cancers, as well as hamsters with nitrosamine-induced pancreatic cancers, were treated with AN-215 or its cytotoxic radical 2-pyrrolinodoxorubicin (AN-201) for 7 to 12 weeks. Tumor growth reduction and survival were analyzed, and cell proliferation rate and apoptosis were examined by histologic methods. Bombesin/GRP receptors on the tumors were studied by ligand-binding assays and their mRNA expression was studied by reverse transcriptase-polymerase chain reaction. Results: All tumors expressed mRNA for subtype 1 bombesin/GRP receptor, but MiaPaCa-2, and in one experiment, SW-1990 tumors did not show binding sites for bombesin. AN-215 powerfully inhibited the growth of all pancreatic cancers that expressed functional receptors for bombesin/GRP. AN-201 was less effective on most tumors and somewhat more toxic than AN-215. Conclusions: Bombesin/GRP receptors are expressed on most ductal pancreatic carcinoma cell lines and can be used for targeted chemotherapy with the cytotoxic bombesin analog AN-215.
| Original language | English |
|---|---|
| Pages (from-to) | 275-282 |
| Number of pages | 8 |
| Journal | Pancreas |
| Volume | 31 |
| Issue number | 3 |
| DOIs | |
| State | Published - Oct 1 2005 |
| Externally published | Yes |
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Keywords
- Bombesin/gastrin-releasing peptide receptor
- Cytotoxic bombesin analog
- Pancreatic carcinoma
- Targeted cancer therapy
ASJC Scopus subject areas
- Gastroenterology
- Endocrinology
Cite this
Inhibition of growth of experimental human and hamster pancreatic cancers in vivo by a targeted cytotoxic bombesin analog. / Szepeshazi, Karoly; Schally, Andrew V; Nagy, Attila; Halmos, Gabor.
In: Pancreas, Vol. 31, No. 3, 01.10.2005, p. 275-282.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Inhibition of growth of experimental human and hamster pancreatic cancers in vivo by a targeted cytotoxic bombesin analog
AU - Szepeshazi, Karoly
AU - Schally, Andrew V
AU - Nagy, Attila
AU - Halmos, Gabor
PY - 2005/10/1
Y1 - 2005/10/1
N2 - Objectives: Targeting anticancer agents to receptors for peptide hormones such as bombesin/gastrin-releasing peptide (GRP) on tumor cells increases the efficacy and lowers the toxicity of cancer therapy. We studied the expression of bombesin/GRP receptors in 6 experimental pancreatic cancers and evaluated tumor inhibition in vivo produced by targeted chemotherapy with the cytotoxic bombesin analog AN-215. Methods: Nude mice with xenografts of Pane-1, CFPAC-1, Capan-1, Capan-2, MiaPaCa-2, and SW-1990 human ductal pancreatic cancers, as well as hamsters with nitrosamine-induced pancreatic cancers, were treated with AN-215 or its cytotoxic radical 2-pyrrolinodoxorubicin (AN-201) for 7 to 12 weeks. Tumor growth reduction and survival were analyzed, and cell proliferation rate and apoptosis were examined by histologic methods. Bombesin/GRP receptors on the tumors were studied by ligand-binding assays and their mRNA expression was studied by reverse transcriptase-polymerase chain reaction. Results: All tumors expressed mRNA for subtype 1 bombesin/GRP receptor, but MiaPaCa-2, and in one experiment, SW-1990 tumors did not show binding sites for bombesin. AN-215 powerfully inhibited the growth of all pancreatic cancers that expressed functional receptors for bombesin/GRP. AN-201 was less effective on most tumors and somewhat more toxic than AN-215. Conclusions: Bombesin/GRP receptors are expressed on most ductal pancreatic carcinoma cell lines and can be used for targeted chemotherapy with the cytotoxic bombesin analog AN-215.
AB - Objectives: Targeting anticancer agents to receptors for peptide hormones such as bombesin/gastrin-releasing peptide (GRP) on tumor cells increases the efficacy and lowers the toxicity of cancer therapy. We studied the expression of bombesin/GRP receptors in 6 experimental pancreatic cancers and evaluated tumor inhibition in vivo produced by targeted chemotherapy with the cytotoxic bombesin analog AN-215. Methods: Nude mice with xenografts of Pane-1, CFPAC-1, Capan-1, Capan-2, MiaPaCa-2, and SW-1990 human ductal pancreatic cancers, as well as hamsters with nitrosamine-induced pancreatic cancers, were treated with AN-215 or its cytotoxic radical 2-pyrrolinodoxorubicin (AN-201) for 7 to 12 weeks. Tumor growth reduction and survival were analyzed, and cell proliferation rate and apoptosis were examined by histologic methods. Bombesin/GRP receptors on the tumors were studied by ligand-binding assays and their mRNA expression was studied by reverse transcriptase-polymerase chain reaction. Results: All tumors expressed mRNA for subtype 1 bombesin/GRP receptor, but MiaPaCa-2, and in one experiment, SW-1990 tumors did not show binding sites for bombesin. AN-215 powerfully inhibited the growth of all pancreatic cancers that expressed functional receptors for bombesin/GRP. AN-201 was less effective on most tumors and somewhat more toxic than AN-215. Conclusions: Bombesin/GRP receptors are expressed on most ductal pancreatic carcinoma cell lines and can be used for targeted chemotherapy with the cytotoxic bombesin analog AN-215.
KW - Bombesin/gastrin-releasing peptide receptor
KW - Cytotoxic bombesin analog
KW - Pancreatic carcinoma
KW - Targeted cancer therapy
UR - http://www.scopus.com/inward/record.url?scp=25844439526&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=25844439526&partnerID=8YFLogxK
U2 - 10.1097/01.mpa.0000175892.97036.a7
DO - 10.1097/01.mpa.0000175892.97036.a7
M3 - Article
C2 - 16163060
AN - SCOPUS:25844439526
VL - 31
SP - 275
EP - 282
JO - Pancreas
JF - Pancreas
SN - 0885-3177
IS - 3
ER -