764981.fig.004a
(a)
764981.fig.004b
(b)
764981.fig.004c
(c)
764981.fig.004d
(d)
Figure 4: Inhibition of p-Akt reversed LX2 coculture induced sorafenib resistance. (a) Signaling pathway changed in LX2 cocultured Huh7. p-ERK, p-Akt, and p-Stat3 increased in LX2 cocultured Huh7. (b) LX2 coculture did not impact c-kit, PDGFR- , and VEGFR-3 protein level. (c) Inhibition of p-Akt by MK-2206 reversed LX2 coculture induced sorafenib resistance. 10 μM MK-2206 was added to the coculture system for 48 h when administrating sorafenib. Cell viability was assessed by MTT assay. MK-2206 reversed coculture induced cell survival while it alone impaired no cell viability. (d) MK-2206 reversed inactivation of caspase cleavage by inhibiting p-Akt. MK-2206 significantly inhibited p-Akt and reactivated PARP and caspase-9 cleavage ( LX2 versus control; LX2 versus LX2 + MK-2206; sora: sorafenib).