|
| Status |
Public on Aug 03, 2012 |
| Title |
EGI-1 cell line treated with Saracatinib vs EGI-1 cell line untreated; EGI-1 xenograft treated with Saracatinib vs EGI-1 untreated |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
Biliary tract carcinoma (BTC) has a poor prognosis due to limited treatment options. There is therefore urgent need to identify new targets and to design innovative therapeutic approaches. Among potential candidate molecules, we evaluated the non-receptor tyrosine kinase Src, observing promising antitumor effects of its small molecule inhibitor Saracatinib in BTC preclinical models. The presence of an active Src protein was investigated by immunohistochemistry in 19 surgical samples from BTC patients. Upon Saracatinib treatment, the phosphorylation of Src and of its downstream transducers was evaluated in the BTC cell lines TFK-1, EGI-1, HuH28 and TGBC1-TKB. The effect of Saracatinib on proliferation and migration was analyzed in these same cell lines, and its antitumor activity was essayed in EGI-1 mouse xenografts. Saracatinib-modulated transcriptome was profiled in EGI-1 cells and in tumor samples of the xenograft model. Src was activated in about 80% of the human BTC samples. In cultured BTC cell lines, low-dose Saracatinib counteracted the activation of Src and of its downstream effectors, increased the fraction of cells in G0/G1 phase, and inhibited cell migration. At high concentrations (median dose from 2.26 to 6.99 µM), Saracatinib was also capable of inhibiting BTC cell proliferation. In vivo, Saracatinib treatment resulted in delayed tumor growth, associated with an impaired vascular network. We here provide a demonstration that the targeted inhibition of Src kinase by Saracatinib is of therapeutic benefit in preclinical models of BTC. We propose our results as a basis for the design of Saracatinib-based clinical applications.
|
| |
|
| Overall design |
EGI-1 cell line treated with Saracatinib at the dose of 10 µM vs EGI-1 cell line untreated; EGI-1 xenograft treated with Saracatinib at the dose of 25 mg/Kg/die vs EGI-1 xenograft untreated
Transcriptional alteration mediated by Saracatinib in vitro and in vivo
|
| |
|
| Contributor(s) |
Cavalloni G, Peraldo-Neia C, Sarotto I, Gammaitoni L, Migliardi G, Soster M, Marchio S, Aglietta M, Leone F |
| Citation(s) |
22452946 |
| Submission date |
Mar 20, 2012 |
| Last update date |
Oct 11, 2016 |
| Contact name |
caterina Peraldo Neia |
| E-mail(s) |
caterina.peraldoneia@gmail.com
|
| Organization name |
Fondazione Edo ed Elvo Tempia
|
| Department |
Laboratory of Cancer Genomics
|
| Lab |
Laboratory of Cancer Genomics
|
| Street address |
via Malta 3
|
| City |
Biella |
| State/province |
Biella |
| ZIP/Postal code |
13900 |
| Country |
Italy |
| |
|
| Platforms (1) |
| GPL14550 |
Agilent-028004 SurePrint G3 Human GE 8x60K Microarray (Probe Name Version) |
|
| Samples (4)
|
|
| Relations |
| BioProject |
PRJNA153711 |
Less...
More...