Hepatic Stellate Cell Coculture Enables Sorafenib Resistance in Huh7 Cells through HGF/c-Met/Akt and Jak2/Stat3 Pathways
Figure 5
Inhibition of p-Stat3 reserved LX2 coculture induced sorafenib resistance. (a) Jak inhibitor tofacitinib reversed LX2 coculture induced sorafenib resistance. 0.25 μM tofacitinib was added to the coculture system for 48 h when administrating sorafenib. Cell viability was assessed by MTT assay. Tofacitinib reversed coculture induced cell survival while it alone impaired no cell viability. (b) Activation of Jak2/Stat3 induced sorafenib resistance whose inhibition activated sorafenib-induced apoptosis. (c) Stat3 inhibitor S3I-201 inhibited cell viability dose-dependently. (d) S3I-201 inhibited phosphorylation of Stat3 and induced apoptosis dose-dependently. (e) Combined administration of sorafenib (20 μM) and S3I-201 (80 μM) augmented cell apoptosis in the presence of LX2 coculture ( sora + S3I-201 versus sora; sora + S3I-201 versus S3I-201; sora: sorafenib).
