| Thioridazine (THO) was originally used to treat psychotic patients. Recently, THOwas shown to inhibit the growth of many cancer cell lines.But its killing effect on livercancer stem cells have not yet been reported. Cancer stem cells play an important rolein tumor metastasis, recurrence and drug resistance. The suspension culture was usedto enrich cancer stem cells in vitro to test killing effect of THO on liver cancer stemcell.Liver cancer cells that cultured in suspension medium are detected similarly to livercancer stem cells in many aspects, including embryonic transcription factorsdependence, drug resistance and cell cycle arrest; which show that it significantlyupregulated the expression of phosphorylated STAT3, NANOG and XIAP, anddecreased expression of albumin proteins. The cytotoxicity of THO on liver cancer stemcells were evaluated by MTT, Western blotting and flow cytometry assay. The resultsindicate that THO can significantly inhibit the proliferation of liver cancer stem cellsand induce caspase-dependent apoptosis; but weakly to liver cancer cells. However, thecombination of THO and doxorubicin hydrochloride(DOX) could more significantlyinhibit the proliferation of liver cancer stem cells and cancer cells.Our results show that THO has a specific strong killing effect on liver cancer stemcells, and may bring new hope for future clinical treatment of liver cance. |
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