1. Antiangiogenic activities and cisplatin-combined antitumor activities of BPR0L075.
- Author
-
Chen CP, Hu CB, Yeh KC, Song JS, Yeh TK, Tung FF, Hwang LL, Tseng HY, Huang YC, Shy HS, Hsieh SH, Shen CC, Wang HS, Hsieh HP, Liou JP, Chao YS, and Chen CT
- Subjects
- Angiogenesis Inhibitors administration & dosage, Animals, Cell Growth Processes drug effects, Cisplatin administration & dosage, Drug Screening Assays, Antitumor, Drug Synergism, Endothelial Cells drug effects, Female, HCT116 Cells, Humans, Indoles administration & dosage, Leukemia P388 drug therapy, Male, Mice, Mice, Inbred DBA, Mice, Nude, Neoplasms pathology, Rats, Rats, Sprague-Dawley, Xenograft Model Antitumor Assays, Angiogenesis Inhibitors pharmacology, Antineoplastic Combined Chemotherapy Protocols pharmacology, Indoles pharmacology, Neoplasms drug therapy
- Abstract
Background: Antimitotic tubulin-binding BPR0L075 is structurally analogous to the vascular-disrupting combretastatin A-4., Materials and Methods: In vitro/in vivo models of endothelial cells cultures, Matrigel plug assay, tumor-bearing nude mice, and murine leukemia cells-inoculated mice were utilized to evaluate BPR0L075 for antiangiogenic and antitumoral activity spectra., Results: BPR0L075 concentration-dependently inhibited proliferation and migration of human umbilical vein endothelial cells (HUVECs), disrupted capillary tube formations of HUVECs and rat aorta endothelial cells, and suppressed in vivo VEGF-mediated angiogenesis in Matrigel plugs in mice. Besides inhibiting the colony growth of cancer cells, BPR0L075 suppressed growth of subcutaneously-xenografted human lung, colorectal, and cervical solid tumors in nude mice. Combination treatments of BPR0L075 plus cisplatin, compared to either agent alone, demonstrated a stronger growth inhibition against the tumor xenografts in nude mice and longer lifespan in the leukemia mice., Conclusion: BPR0L075 is an antitumoral and antiangiogenic agent and potentiates the anticancer activity of cisplatin.
- Published
- 2010