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.