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Updated: Feb 11, 2026
The Measurement and Treatment of Suppression in Amblyopia
Published on: December 14, 2012
Endostar, a Modified Endostatin Induces Vascular Normalization to Improve Chemotherapy Efficacy Through Suppression
Min Yu1, Yao Han2, Hongyu Zhuo3
11 Department of Thoracic Oncology, West China Hospital, Sichuan University , Chengdu, China .
Abstract:
Pathological angiogenesis can be a significant barrier to effective cancer therapy. Recent evidence suggests that Endostar may induce vascular normalization, thereby improving tumor perfusion and systemic chemotherapy. However, the molecular mechanism by which Endostar makes chemotherapy more effective remains to be fully elucidated. In this study, established 4T1 breast tumor-bearing animals treated with Endostar were evaluated at serial time points for treatment-associated changes in vascular architecture. As a result, Endostar induced a morphologically and functionally normalized vascular network. Combined Endostar and doxorubicin exhibited significant antitumor (34% of control size) and antimetastatic effects (29% of control metastatic nodules) in vivo. Finally, a two-dimensional gel electrophoresis and MALDIQ-TOF MS/MS-based proteomics approach was used to identify differentially expressed proteins involved in vascular normalization during Endostar administration. SRCIN1 was detected as one of the most significantly increased proteins. SRCIN1 is a novel Src-binding protein that regulates Src activation through C-terminal Src kinase, and attenuated Src activation during Endostar treatment was further confirmed by immunoblotting. Collectively, these data provided a molecular basis for vascular normalization, which were associated with the observed synergistic effect in vivo.
Insights
Endostar promotes vascular normalization in breast tumors, enhancing chemotherapy effectiveness. This study identified SRCIN1 as a key protein involved in Endostar
Area of Science:
- Oncology
- Vascular Biology
- Molecular Biology
Background:
- Pathological angiogenesis hinders effective cancer therapy.
- Endostar may normalize tumor vasculature, improving chemotherapy.
- The precise molecular mechanism of Endostar's efficacy is unclear.
Purpose of the Study:
- To investigate the molecular mechanisms underlying Endostar-induced vascular normalization.
- To evaluate the combined efficacy of Endostar and doxorubicin in breast cancer models.
- To identify proteins associated with vascular normalization during Endostar treatment.
Main Methods:
- 4T1 breast tumor model in animals treated with Endostar.
- Analysis of vascular architecture changes over time.
- Proteomic analysis using 2D gel electrophoresis and MALDI-Q-TOF MS/MS.
- Immunoblotting to confirm protein expression and activity.
Main Results:
- Endostar treatment led to morphologically and functionally normalized tumor vasculature.
- Combined Endostar and doxorubicin showed significant antitumor and antimetastatic effects.
- SRCIN1 was identified as a significantly upregulated protein.
- Endostar treatment attenuated Src activation, confirmed by immunoblotting.
Conclusions:
- Endostar induces vascular normalization, providing a molecular basis for its synergistic effect with chemotherapy.
- SRCIN1 is implicated in the vascular normalization process mediated by Endostar.
- Targeting vascular normalization presents a promising strategy for enhancing cancer therapy.
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