Hepatic Stellate Cell Coculture Enables Sorafenib Resistance in Huh7 Cells through HGF/c-Met/Akt and Jak2/Stat3 Pathways
Figure 1
HSC-LX2 coculture induced sorafenib resistance in Huh7. (a) The inhibitory effect of sorafenib on Huh7 cells. After 48 h of sorafenib exposure at different concentrations, cell viability was assessed by MTT assay. Sorafenib could impair Huh7 cell viability at the concentration equal to and more than 10 μM. (b) Sorafenib-induced apoptosis in Huh7. After 48 h of sorafenib exposure at different concentrations, cell apoptosis was assessed by Western blotting. (c) HSC-LX2 coculture attenuated sorafenib-induced cell suppression. Huh7 cells were cocultured with LX2 for 48 h before the administration of sorafenib for another 48 h. Cell viability was assessed by MTT assay which showed attenuated cell death in cocultured group. (d) HSC-LX2 coculture attenuated sorafenib-induced apoptosis by increasing antiapoptotic proteins. Cell lysates were subjected to Western blotting after sorafenib administration for 48 h. HSC-LX2 coculture decreased cleavage of caspases and PARP (left panel). HSC-LX2 coculture increased expression levels of antiapoptotic proteins Mcl-1 and Bcl-2 (right panel) (; sora: sorafenib).
