Chen N Y, Holle L, Li W, Peirce S K, Beck M T, Chen W Y
Oncology Research Institute, Cancer Center, Greenville Hospital System, Department of Microbiology and Molecular Medicine, Clemson University, Greenville, SC 29605, USA.
Int J Oncol. 2002 Apr;20(4):813-8. doi: 10.3892/ijo.20.4.813.
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.
此前我们证明，在第129位氨基酸处有单个氨基酸替换的突变型人催乳素（hPRL）（hPRL-G129R）能够通过诱导凋亡来抑制人乳腺癌细胞增殖。在本研究中，我们报告了hPRL-G129R在携带人乳腺癌异种移植物（T-47D和MCF-7）的裸鼠体内的抗肿瘤作用。为了延长蛋白质的半衰期，hPRL或hPRL-G129R分别与生长因子减少的基质胶配制或制成缓释微丸（定制的5mg/5天释放）。最初，给接种了（皮下）T-47D人乳腺癌细胞的裸鼠用与基质胶配制的hPRL或hPRL-G129R进行治疗。在为期7周的研究结束时，发现hPRL显著刺激了T-47D异种移植物的体内生长（平均肿瘤体积，202±62mm³，而对照小鼠为124±31mm³），而hPRL-G129R抑制了肿瘤生长（平均肿瘤体积，79±32mm³）。在第二个实验中，使用携带MCF-7人乳腺癌异种移植物并接受含hPRL-G129R缓释微丸治疗的裸鼠，进一步证实了hPRL-G129R的抑制作用。基于这些结果，我们相信hPRL-G129R在不久的将来可用于改善人类乳腺癌的治疗效果。
