Figure 1
Chondrosarcoma cell lines are not sensitive to PKC inhibition. (A) Schematic representation of activation of PI3K and Src pathway by RTKs. Receptor tyrosine kinases can activate PKC, phosphatidylinositol 3-kinase (PI3K) and Src. PKC and Src can also activate the PI3K/AKT/GSK3β pathway, promoting survival, proliferation and migration. The Src pathway activates the Ras/Raf pathway. Enzastaurin is a selective PKC inhibitor also reported to inhibitin activating phosphorylation of GSK3β. Dasatinib is a Src inhibitor. Adapted from Fizazi (2007). (B) HeLa cell line showing 70% decrease in cell viability after treatment with enzastaurin. Chondrosarcoma cell lines poorly respond to enzastaurin alone, and an additive effect is observed when alternating 10 μ M doxorubicin (DXR) and 10 μ M enzastaurin (Enz) for 24 h each for 72 h in total. No difference is observed when order of administration is reversed. Significant difference between TP53 mutant and wild-type cell lines (P=0.002). (C) Combination of enzastaurin with Src inhibitor dasatinib (Das) showing additive effect in chondrosarcoma cell lines. No significant difference is observed between TP53 mutant and wild-type cell lines (P=0.38).
