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Published on: September 8, 2017
Comparison of antiangiogenic activities using paclitaxel (taxol) and docetaxel (taxotere)
Derrick S Grant1, Torian L Williams, Michael Zahaczewsky
1Cardeza Foundation for Hematologic Research, Department of Medicine, Thomas Jefferson University, Philadelphia, PA 19107-5097, USA.
Abstract:
Tumor growth requires a competent vascular supply and angiogenesis has been considered as a potential target for the treatment of several cancers. The two clinically approved taxanes, paclitaxel and docetaxel, are novel antimitotic agents that are under extensive investigation in clinical trials. Both taxanes have demonstrated significant activity against many solid tumors, but little is known about the effect of paclitaxel and docetaxel on endothelial cell function and angiogenic processes. The purpose of our study was to examine and compare the effects of these drugs on angiogenic processes in vitro and in vivo. These processes include: proliferation, migration and differentiation of cultured human umbilical vein endothelial cells (HUVEC) (in vitro), capillary sprouting of rat aortic ring explants (ex vivo) and HT1080 tumor growth in vivo. Our results demonstrate that endothelial cells are 10-100-fold more sensitive to these drugs than tumor cells. Additionally, comparison of the taxanes demonstrated that angiogenesis is blocked by both drugs primarily via inhibition of proliferation and differentiation (tube assay) and induction of cell death. Docetaxel, however, appears to be more potent at inhibiting angiogenesis, with an IC(50) concentration 10x less than that of paclitaxel. We conclude that these important findings should be taken in account in clinical trials where tumor angiogenesis is being targeted.
Insights
Paclitaxel and docetaxel inhibit tumor angiogenesis by affecting endothelial cell proliferation and differentiation. Docetaxel is more potent than paclitaxel in blocking these angiogenic processes.
Area of Science:
- Oncology
- Vascular Biology
- Pharmacology
Background:
- Tumor growth depends on angiogenesis, the formation of new blood vessels.
- Angiogenesis is a validated therapeutic target for cancer treatment.
- Taxanes (paclitaxel, docetaxel) are anticancer drugs with limited known effects on angiogenesis.
Purpose of the Study:
- To compare the effects of paclitaxel and docetaxel on angiogenic processes.
- To investigate drug impact on endothelial cell function and tumor growth.
Main Methods:
- In vitro studies using human umbilical vein endothelial cells (HUVEC) for proliferation, migration, and differentiation.
- Ex vivo analysis of capillary sprouting in rat aortic ring explants.
- In vivo assessment of HT1080 tumor growth.
Main Results:
- Endothelial cells were 10-100 times more sensitive to taxanes than tumor cells.
- Both drugs inhibited angiogenesis by reducing proliferation and differentiation and inducing cell death.
- Docetaxel demonstrated higher potency, with a 10-fold lower IC50 than paclitaxel.
Conclusions:
- Paclitaxel and docetaxel effectively inhibit angiogenesis through multiple mechanisms.
- Docetaxel exhibits superior anti-angiogenic activity compared to paclitaxel.
- Findings are relevant for clinical trials targeting tumor angiogenesis.
