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The microtubule-affecting drug paclitaxel has antiangiogenic activity
Abstract:
Endothelial cell migration is a critical event during angiogenesis, and inhibitors of cell motility can affect the angiogenic process. Paclitaxel (Taxol(R)), a microtubule-stabilizing antineoplastic cytotoxic drug, inhibits motility and invasiveness of several cell types. The aim of this study was to investigate the effect of paclitaxel on endothelial cell functions and on angiogenesis. In vivo, paclitaxel (20-28 mg/kg i.v.) significantly inhibited the angiogenic response induced by tumor cell supernatant embedded in a pellet of reconstituted basement membrane (Matrigel) injected s.c. into C57BL/6N mice. In vitro, paclitaxel inhibited endothelial cell proliferation, motility, invasiveness, and cord formation on Matrigel in a dose-dependent manner. The antiangiogenic activity of paclitaxel was not linked to its cytotoxicity, since inhibition of endothelial cell chemotaxis and invasiveness occurred at drug concentrations which did not affect endothelial cell proliferation. Another cytotoxic drug, cisplatin, that inhibited endothelial cell proliferation in vitro, did not affect angiogenesis in vivo. These data indicate that paclitaxel has a strong antiangiogenic activity, a property that might contribute to its antineoplastic activity in vivo.
Insights
Paclitaxel inhibits endothelial cell functions and angiogenesis, a key process in tumor growth. This anti-angiogenic activity may contribute to its effectiveness as an anti-cancer drug.
Area of Science:
- Oncology
- Cell Biology
- Pharmacology
Background:
- Endothelial cell migration is crucial for angiogenesis.
- Paclitaxel (Taxol) is a cytotoxic drug that inhibits cell motility.
- Understanding paclitaxel's effect on angiogenesis is important for cancer therapy.
Purpose of the Study:
- To investigate the impact of paclitaxel on endothelial cell functions.
- To evaluate paclitaxel's effect on angiogenesis in vivo and in vitro.
Main Methods:
- In vivo studies using C57BL/6N mice with Matrigel plugs containing tumor cell supernatant.
- In vitro assays assessing endothelial cell proliferation, motility, invasiveness, and cord formation.
- Comparison with cisplatin, another cytotoxic drug.
Main Results:
- Paclitaxel significantly inhibited angiogenesis in vivo.
- In vitro, paclitaxel dose-dependently inhibited endothelial cell proliferation, motility, invasiveness, and cord formation.
- Anti-angiogenic effects were observed at non-cytotoxic concentrations for endothelial cell proliferation.
Conclusions:
- Paclitaxel exhibits potent anti-angiogenic activity.
- This anti-angiogenic property may contribute to paclitaxel's antineoplastic effects.
- Paclitaxel's mechanism differs from cisplatin's, highlighting specific anti-angiogenic actions.