In vivo studies of the anti-tumor effects of a human prolactin antagonist, hPRL-G129R.

Abstract

Previously we demonstrated that a mutated human prolactin (hPRL) with a single amino acid substitution at position 129 (hPRL-G129R) was able to inhibit human breast cancer cell proliferation via the induction of apoptosis. In this study, we report the in vivo anti-tumor effects of hPRL-G129R in nude mice bearing human breast cancer xenografts (T-47D and MCF-7). In an effort to prolong the half-life of the proteins, hPRL or hPRL-G129R were formulated with either growth factor reduced Matrigel or into slow-releasing pellets (custom made 5 mg/5 day release). Initially, nude mice inoculated (s.c.) with T-47D human breast cancer cells were treated with either hPRL or hPRL-G129R formulated with Matrigel. At the end of the 7-week study, it was found that hPRL significantly stimulated the in vivo growth of T-47D xenografts (mean tumor volume, 202 +/- 62 mm(3) as compared to 124 +/- 31 mm(3) in control mice), whereas hPRL-G129R inhibited the tumor growth (mean tumor volume, 79+/-32 mm3). The inhibitory effects of hPRL-G129R were further confirmed in a second experiment using nude mice bearing MCF-7 human breast cancer xenografts and treated with slow-releasing pellets containing hPRL-G129R. Based on these results, we believe that hPRL-G129R can be used to improve the outcome of human breast cancer treatment in the near future.

• Authors: N Y Chen, L Holle, W Li, S K Peirce, M T Beck, W Y Chen
• Journal: International journal of oncology (Int J Oncol) Vol. 20 Issue 4 Pg. 813-8 (Apr 2002) ISSN: 1019-6439 [Print] Greece
• PMID: 11894130 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antineoplastic Agents
• Drug Combinations
• Drug Implants
• Hormone Antagonists
• Laminin
• Proteoglycans
• Receptors, Prolactin
• prolactin, Arg(129)-
• matrigel
• Prolactin
• Collagen

Topics

• Animals
• Antineoplastic Agents (therapeutic use)
• Collagen (chemistry)
• Drug Combinations
• Drug Delivery Systems
• Drug Implants (metabolism)
• Female
• Hormone Antagonists (therapeutic use)
• Humans
• Laminin (chemistry)
• Mammary Neoplasms, Experimental (drug therapy, metabolism, pathology)
• Mice
• Prolactin (antagonists & inhibitors, metabolism, therapeutic use)
• Proteoglycans (chemistry)
• Radioligand Assay
• Receptors, Prolactin (metabolism)
• Tissue Distribution
• Tumor Cells, Cultured (drug effects)