Hepatic Stellate Cell Coculture Enables Sorafenib Resistance in Huh7 Cells through HGF/c-Met/Akt and Jak2/Stat3 Pathways

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-𝛽, 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 (^∗𝑃<0.05 LX2 versus control; ^#𝑃<0.05 LX2 versus LX2 + MK-2206; sora: sorafenib).

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