Abstract
Background: Antimitotic tubulin-binding BPR0L075 is structurally analogous to the vascular-disrupting combretastatin A-4. Materials and Methods: In vitrei 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.
| Original language | English |
|---|---|
| Pages (from-to) | 2813-2822 |
| Number of pages | 10 |
| Journal | Anticancer Research |
| Volume | 30 |
| Issue number | 7 |
| Publication status | Published - Jul 2010 |
Keywords
- Angiogenesis
- Cisplatin
- Combretastatin
- Microtubule
- Vascular disrupting agent
ASJC Scopus subject areas
- Oncology
- Cancer Research
