Fig 4.tif (1.23 MB)
Pharmacodynamic effects of dasatinib on the Src pathway.
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posted on 2017-11-01, 17:38 authored by 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. MessersmithA) 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.
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Src pathwayanti-proliferative activity72 hours17 CRC explantsSrc expressiondasatinib treatmentCRC explantsG 1 inhibitionbaseline increaseanti-tumor effectsMethods CRC cell lines50 CRC cell linestumor growth inhibitionanti-invasive activityvivo efficacyG 1 cell cycle arrestsulforhodamine Bexplant mouse model Background DysregulationFAK gene expression17 patient-derived CRC explantsSRBxenograft mouse modelanti-tumor activityPDXpatient-derived tumor explantConclusion DasatinibCRC cell linesTGIcolorectal cancer cell linesIC28 days
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