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Opioid growth factor (OGF) inhibits human pancreatic cancer transplanted into nude mice
I S Zagon1, S D Hytrek, J P Smith
1Department of Neuroscience and Anatomy, Pennsylvania State University, Milton S. Hershey Medical Center, Hershey 17033, USA. iszl$@psuvm.psu.edu
Abstract:
Nude mice inoculated with human pancreatic cancer (BxPC-3) cells and receiving 5 mg/kg of opioid growth factor ([Met5]enkephalin; OGF) three times daily exhibited a marked retardation in tumorigenicity compared to animals injected with sterile water (controls). OGF-treated animals had a delay of 43% in initial tumor appearance compared to control subjects (10.6 days). At the time when all of the control mice had tumors, 62% of the mice in the OGF group had no signs of neoplasia. Tumor tissue excised from mice after 30 days was assayed for levels of [Met5]enkephalin and zeta opioid receptors. Tumor tissue levels of [Met5]enkephalin were 24-fold greater in OGF-treated mice than controls, but plasma levels of OGF were 8.6-fold lower in animals receiving OGF. Specific and saturable binding of radiolabeled [Met5]enkephalin to nuclear homogenates of pancreatic tumor tissue was recorded, with a binding affinity (Kd) of 10 nM and a binding capacity (Bmax) of 46.8 fmol/mg protein. Binding capacity, but not affinity, of [3H-Met5]enkephalin was reduced by 58% of control levels in tumor tissue from mice of the OGF group. OGF and the zeta (zeta) opioid receptor were detected in human pancreatic tumor cells by immuno-cytochemistry. These results demonstrate that an endogenous opioid and its receptor are present in human pancreatic cancer, and act as a negative regulator of tumorigenesis in vivo.
Insights
Opioid growth factor ([Met5]enkephalin; OGF) significantly slowed pancreatic cancer growth in mice. This endogenous opioid and its receptor act as a negative regulator of tumorigenesis, offering potential therapeutic insights.
Area of Science:
- Oncology
- Neuroendocrinology
- Molecular Biology
Background:
- Human pancreatic cancer (BxPC-3) cells were used to establish tumors in nude mice.
- Opioid growth factor ([Met5]enkephalin; OGF) is an endogenous opioid peptide.
- Zeta (ζ) opioid receptors are implicated in cellular regulation.
Purpose of the Study:
- To investigate the role of OGF and its receptor in pancreatic cancer tumorigenesis in vivo.
- To determine if OGF administration affects tumor development and growth.
- To characterize OGF and zeta opioid receptor presence and binding in pancreatic tumors.
Main Methods:
- Nude mice were inoculated with human pancreatic cancer cells and treated with OGF or sterile water.
- Tumor appearance and growth were monitored over time.
- Levels of OGF and zeta opioid receptors in tumor tissue and plasma were measured.
- Radioligand binding assays were performed on nuclear homogenates of tumor tissue.
- Immunocytochemistry was used to detect OGF and zeta opioid receptors in tumor cells.
Main Results:
- OGF treatment significantly retarded tumor growth, delaying initial appearance by 43%.
- At 30 days, 62% of OGF-treated mice showed no signs of neoplasia compared to controls.
- Tumor tissue OGF levels were 24-fold higher in OGF-treated mice, while plasma OGF levels were lower.
- Specific binding of [Met5]enkephalin to nuclear tumor homogenates indicated the presence of zeta opioid receptors.
- Binding capacity of [3H-Met5]enkephalin was reduced by 58% in OGF-treated mice, suggesting receptor modulation.
- OGF and zeta opioid receptors were confirmed in human pancreatic tumor cells via immunocytochemistry.
Conclusions:
- An endogenous opioid, OGF, and its receptor are present in human pancreatic cancer.
- OGF acts as a negative regulator of pancreatic tumorigenesis in vivo.
- These findings suggest a potential therapeutic role for OGF in managing pancreatic cancer.