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Updated: Apr 25, 2026
Long-term Live-cell Imaging to Assess Cell Fate in Response to Paclitaxel
Published on: May 14, 2018
Src inhibition potentiates antitumoral effect of paclitaxel by blocking tumor-induced angiogenesis
Simona Delle Monache1, Patrizia Sanità1, Alessia Calgani1
1Dipartimento di Scienze Cliniche Applicate e Biotecnologiche, University of L׳Aquila, via Vetoio Coppito, 67100 L׳Aquila, Italy.
Abstract:
The protein kinase Src is frequently over-activated in advanced cancers where it modulates the signaling transduction cascade of several growth factors. The feasibility of combination treatment of Src inhibitors with chemotherapy is currently under investigation. We evaluated the anti-tumoral effect of paclitaxel (PTX) in combination with S13, a tyrosine kinase inhibitor with a prevalent specificity for Src, in a hormone-insensible prostate cancer (PCa) cell model. In vivo, combination treatment with PTX and S13 reduced dramatically PCa tumor growth with a relevant difference in the density of new blood vessels with respect to control and single treatments. This reduction was determined by a concomitant impairment of endothelial cell migration and of VEGF release by cancer cells. In fact, S13, when used alone, was sufficient to reduce tubule formation in vivo, and to inhibit VEGFR2 activation and FAK expression in endothelial cells. In addition, the combination treatment determined a significant reduction in ROS production and HIF-1 stabilization in PCa cells respect to single treatments with S13 or PTX. In conclusion, Src-inhibition could be an effective therapeutic strategy aimed at supporting the anti-angiogenic action of PTX in aggressive PCa.
Insights
Combining paclitaxel (PTX) with Src inhibitor S13 significantly reduced prostate cancer growth and new blood vessel formation. This combination therapy offers a promising strategy for aggressive prostate cancer by targeting angiogenesis.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Protein kinase Src is often over-activated in advanced cancers, influencing growth factor signaling.
- Combination treatments of Src inhibitors with chemotherapy are being explored for cancer therapy.
Purpose of the Study:
- To evaluate the anti-tumoral effect of combining paclitaxel (PTX) with the Src inhibitor S13 in a hormone-insensible prostate cancer (PCa) model.
- To investigate the impact of this combination on tumor growth, angiogenesis, and related molecular pathways.
Main Methods:
- In vivo evaluation of PTX and S13 combination treatment in a PCa cell model.
- Assessment of tumor growth, new blood vessel density, endothelial cell migration, and VEGF release.
- Analysis of S13's effect on tubule formation, VEGFR2 activation, FAK expression, ROS production, and HIF-1 stabilization.
Main Results:
- Combination treatment dramatically reduced PCa tumor growth and new blood vessel density compared to single treatments.
- The combination impaired endothelial cell migration and VEGF release.
- S13 alone inhibited in vivo tubule formation, VEGFR2 activation, and FAK expression; the combination further reduced ROS production and HIF-1 stabilization.
Conclusions:
- Src inhibition, via S13, supports the anti-angiogenic effects of PTX in aggressive prostate cancer.
- Combining Src inhibitors with chemotherapy like PTX is a viable therapeutic strategy for advanced prostate cancer.
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