Li Mingyuan,Xu Yanmin,Qian Cheng.Effect of sorafenib on inhibiting growth of hepatocellular carcinoma cells and analysis of biological characteristics of sorafenib-resistant cells[J].J Amry Med Univ (J Third Mil Med Univ),2016,38(06):580-584.
Li Mingyuan,Xu Yanmin,Qian Cheng.Effect of sorafenib on inhibiting growth of hepatocellular carcinoma cells and analysis of biological characteristics of sorafenib-resistant cells[J].J Amry Med Univ (J Third Mil Med Univ),2016,38(06):580-584.DOI:
Objective To determine the effect of sorafenib on inhibiting growth of hepatocellular carcinoma (HCC) cell lines Huh-7 and PLC/PRF/5
and primary cell lines T1115 and T1224
and further investigate the biological characteristics of sorafenib-resistant cells. Methods Sorafenib-resistant cell model PLC/PRF/5 was established through long-term treatment with 10 μmol/L sorafenib. MTS and colony formation assays were used to detect the proliferation of different cell lines under different concentrations of sorafenib. The expression of p-AKT
p-STAT3
and pluripotency related genes (Nanog
Sox2 and Oct4) were detected by Western blotting. The expression of multidrug resistance gene ABCC1 was detected by RT-PCR. The migration ability of sorafenib-resistant cells and their parental counterparts was detected by Transwell assay and wound healing assay. Results The data showed that the inhibitory effect of sorafenib on HCC cells and primary cells was enhanced with the sorafenib concentration increase
and the expression of p-STAT3 and p-AKT were down-regulated after sorafenib treatment. Furthermore
sorafenib-resistant cell model was successfully established. The proliferation of sorafenib-resistant cells was significantly decreased compared with the parental counterparts
but the migration ability was significantly strengthened. The results also demonstrated that the expression of ABCC1
Nanog
Sox2 and Oct4 were up-regulated in the sorafenib-resistant cells. Conclusion Sorafenib can effectively inhibit the growth of HCC cells
and the sorafenib-resistant cells have strong migration ability and cancer stem cell-like properties.