Discussion On this report, we first demonstrated the heterogeneous sensitivity of 9 HCC cell lines to dasatinib in vitro as proven by their IC50 values. Our research also showed the growth inhibition by dasatinib was correlated with t Src in 7 9 cell lines and the p Src t Src ratios were signifi cantly decrease in sensitive cells than resistant cells in the similar 7 9 cell lines. In 6 resistant cell lines the growth in hibition this content by dasatinib was related to unique action of Src protein by p Src t Src ratio. With the exception of PLC PRF 6, there was an inverse correlation involving t Src and t EGFR. Song et al. showed that dasatinib treatment method resulted in apoptosis in gefitinib delicate EGFR mutant lung cancer cells in vitro Their findings have been also confirmed by other investigators not long ago Our re sults showed even in gefitinib resistant HCC cell lines some have been nonetheless sensitive to dasatinib.
There was also a co overexpression with Src and members of EGFR fam ily in breast cancer Our findings that EGFR expres sion influenced the response of HCC cells to dasatinib even further strengthened the notion that a different cross talk mechanism may exist amongst Src family and Motesanib EGFR loved ones tyrosine kinases in hepatocarcinogenesis. These two TK signaling pathways may well plement each and every other from the oncogenic system and development of resistance to remedy of both pathway. Our effects advised bination of inhibitors of the two pathways could yield superior results, as we’ve got proven synergistic interaction involving dasatinib and gefitinib in HCC cells on our earlier study The preliminary research of dasatinib and erlotinib bination in 29 evaluable patients with re present or metastatic non tiny cell lung cancer showed 2 partial response and 62% sickness control charge Even more scientific studies are required to discover the optimal bination and the suitable clinical settings. Baseline t Src and exact Src exercise may possibly be used as helpful predictive biomarkers for picking dasatinib treatment in HCC patients. We also showed in most of cell lines, dasatinib suppressed the expression of p Src, p FAK and p Akt which correlated with all the level of growth inhibition.