Endostar, a Modified Endostatin Induces Vascular Normalization to Improve Chemotherapy Efficacy Through Suppression of Src Signaling Pathway
| Autor: | Shuang Zhang, Hongyu Zhuo, Min Yu, Yao Han |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Cancer Research Angiogenesis medicine.medical_treatment Angiogenesis Inhibitors Proteomics 03 medical and health sciences 0302 clinical medicine In vivo Cell Line Tumor medicine Animals Humans Radiology Nuclear Medicine and imaging Doxorubicin Pharmacology Chemotherapy Mice Inbred BALB C Chemistry General Medicine Endostatins Disease Models Animal 030104 developmental biology Oncology 030220 oncology & carcinogenesis Cancer research Female Endostatin Signal transduction Proto-oncogene tyrosine-protein kinase Src medicine.drug Signal Transduction |
| Zdroj: | Cancer biotherapyradiopharmaceuticals. 33(4) |
| ISSN: | 1557-8852 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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