Example 6

It is well known that BRAF inhibitor PLX4032 can induce paradoxical MAPK activation and cause abnormal cell proliferation in RAS mutation cells. The expression level of MAPK signaling pathway related proteins in PDV cells was examined by western blotting (FIG. 7). PLX4032 at 0.5 μM promoted p-MEK and p-ERK protein expression at 6-24 h treatment. MEK inhibitor, AZD6244 reversed the up-regulation of p-ERK induced by PLX4032, while KWM-EO, LM-EO at 75 μg/mL and L+C at 60 μg/mL significantly abolished the p-MEK and p-ERK protein expression in PLX4032-stimulated PDV cells. KWM-EO, LM-EO and L+C treatment also decreased the expression of MEK but not ERK.

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