Pharmacodynamic effects of dasatinib on the Src pathway.
Aaron J. Scott
Eun-Kee Song
Stacey Bagby
Alicia Purkey
Martin McCarter
Csaba Gajdos
Kevin S. Quackenbush
Benjamin Cross
Todd M. Pitts
Aik Choon Tan
S. Gail Eckhardt
Hubert Fenton
John Arcaroli
Wells A. Messersmith
10.1371/journal.pone.0187173.g004
https://plos.figshare.com/articles/figure/Pharmacodynamic_effects_of_dasatinib_on_the_Src_pathway_/5560561
<p>A) Treatment with dasatinib (0.8 μmol/L) at 0.5h, 1h, 2h, 4h, and 8h significantly reduced the activation of Src, FAK and paxillin at all time points examined in the HCT116 sensitive CRC cell line when compared to control. B) A decrease in Src activity was seen in 1 out of 3 CRC explants treated with dasatinib in the sensitive (CRC036) and resistant CRC explant (CRC027) measured at end of study (day 28). However, in both cases FAK activity appeared to be increased.</p>
2017-11-01 17:38:02
Src pathway
anti-proliferative activity
72 hours
17 CRC explants
Src expression
dasatinib treatment
CRC explants
G 1 inhibition
baseline increase
anti-tumor effects
Methods CRC cell lines
50 CRC cell lines
tumor growth inhibition
anti-invasive activity
vivo efficacy
G 1 cell cycle arrest
sulforhodamine B
explant mouse model Background Dysregulation
FAK gene expression
17 patient-derived CRC explants
SRB
xenograft mouse model
anti-tumor activity
PDX
patient-derived tumor explant
Conclusion Dasatinib
CRC cell lines
TGI
colorectal cancer cell lines
IC
28 days