In vivo studies of the anti-tumor effects of a human prolactin antagonist, hPRL-G129R.
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.
Chen
N Y
NY
Oncology Research Institute, Cancer Center, Greenville Hospital System, Department of Microbiology and Molecular Medicine, Clemson University, Greenville, SC 29605, USA.
Holle
L
L
Li
W
W
Peirce
S K
SK
Beck
M T
MT
Chen
W Y
WY
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D003094:Collagen / Q000737:chemistry; D004338:Drug Combinations; D016503:Drug Delivery Systems; D004343:Drug Implants / Q000378:metabolism; D005260:Female; D006727:Hormone Antagonists / Q000627:therapeutic use*; D006801:Humans; D007797:Laminin / Q000737:chemistry; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D011388:Prolactin / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000627:therapeutic use*; D011509:Proteoglycans / Q000737:chemistry; D011869:Radioligand Assay; D011981:Receptors, Prolactin / Q000378:metabolism; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D004338:Drug Combinations; D004343:Drug Implants; D006727:Hormone Antagonists; D007797:Laminin; D011509:Proteoglycans; D011981:Receptors, Prolactin; C402398:prolactin, Arg(129)-; C059485:matrigel; D011388:Prolactin; D003094:Collagen