Targeted Antivascular Therapy with the Apolipoprotein(a) Kringle V, rhLK8, Inhibits the Growth and Metastasis of Human Prostate Cancer in an Orthotopic Nude Mouse Model

• DOI: 10.1593/neo.12380
• Publication Date: 2015-04-23T13:07:58Z
• Authors: Ho-Jeong Lee; Hyun-Kyung Yu; John N. Papadopoulos; Seung Wook Kim; Junqin He; Yong-Keun Park; Yeup Yoon; Jang-Seong Kim; Sun Jin Kim
• Keywords: Male; 0301 basic medicine; Paclitaxel; Neoplasms. Tumors. Oncology. Including cancer and carcinogens; Mice, Nude; Prostatic Neoplasms; Angiogenesis Inhibitors; Xenograft Model Antitumor Assays; Peptide Fragments; Recombinant Proteins; 3. Good health; Disease Models, Animal; Mice; 03 medical and health sciences; Kringles; Animals; Humans; Neoplasm Metastasis; RC254-282; Apolipoproteins A

Antivascular therapy has emerged as a rational strategy to improve the treatment of androgen-independent prostate cancer owing necessity establishing vascular network for growth and progression primary metastatic tumor. We determined whether recombinant human apolipoprotein(a) kringle V, rhLK8, produces therapeutic efficacy in an orthotopic animal model. Fifty thousand cells (PC-3MM2) were injected into nude mice. After 3 days, these mice randomized receive vehicle solution (intraperitoneally [i.p.], daily), paclitaxel (8 mg/kg i.p., weekly), rhLK8 (50 or combination 4 weeks. Treatment with alone did not show significant effects on tumor incidence size compared control group. The significantly reduced lymph node metastasis. Significant reduction microvessel density cellular proliferation induction apoptosis cells, tumor-associated endothelial also achieved. Similarly, PC-3MM2 tumors growing tibia showed suppression metastasis by paclitaxel. integrity bone was preserved, increased. In conclusion, results suggest that targeting microenvironment antivascular effect combined conventional cytotoxic chemotherapy could be new effective approach their metastases.