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      • Synergistic Activity of Paclitaxel and Sorafenib Against Liver Cancer Stem Cells

        ( Hend M. Nawara ),( Said M. Afify ),( Ghmkin Hassan ),( Maram H. Zahra ),( Marwa N. Atallah ),( Hager Mansour ),( Hagar A. Abu Quora ),( Amira Osman ),( Hiroki Kakuta ),( Hiroki Hamada ),( Akimasa Se 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1

        Aims: Cancer stem cells (CSCs), also known as tumor-initiating cells (TICs), are suggested to be responsible for drug resistance and cancer recurrence. Current treatments with conventional chemotherapy are not highly efficient against the cancer stem cells (CSCs). The combination of anticancer drugs, of which functions are different from the other, enhances efficiency compared to the mono-therapy because it targets cancer cells in a synergistic or an additive manner. In this study, the effect of paclitaxel and sorafenib on cancer stem cells (CSCs) developed from mouse iPSCs in very low concentration was evaluated. Methods: To investigate the effect of combination therapy, CSCs were exposed to paclitaxel and/or sorafenib at different concentrations of 1, 2 and 4 nM, respectively. Cell viability was assessed with 3-(4,5-dimethylthiazolyl)-2,5-diphenyltetrazolium bromide (MTT). The same concentrations of the agents were assessed for the effect on the self-renewal potential of CSCs subpopulation by sphere formation ability. Results: As a result, a combination of sorafenib and paclitaxel significantly reduced the resistance while the CSCs exhibited drug resistance against paclitaxel alone. Also, combination of these agents reduces the self-renewal potential of CSCs when compared to single treatment. Simultaneously, combination significantly suppressed not only the colony formation but also the tube formation of the Cancer stem cells. Conclusions: These results suggest the combination therapy of paclitaxel and sorafenib in low doses be an attractive approach to target cancer stem cells in the future.

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