P-glycoprotein is not involved in pathway of Fas-induced apoptosis
We verify whether P-glycoprotein (P-gp) could induce cell resistance to apoptosis by inhibiting caspase-8 and caspase-3. Human KB cells, either drug-sensitive or with multidrug resistance (MDR) phenotype caused by Over-expression of P-gp (KBv200 cells), were treated with anti-Fas (CH-11) to induce apoptosis. Cytotoxicity was detected by MTT assay. Symptoms of cell death were assessed by morphological observation after Hoechst33258 staining, activation of caspase-8 and caspase-3 was measured by Western blotting.Compared with KB cells, the resistance of KBv200 cells to VCR (vincristine) was about 51-fold higher.Anti-Fas (CH-11) induced cytotoxicity and apoptosis in both sensitive KB cells and MDR phenotype KBv200 cells. The IC50 of CH-11 in KB cells was similar to that in KBv200 cells. CH-11 induced similar apoptotic rates in both KB cells and KBv200 cells, which could be classified as caspase-dependent apoptotic pathway. Verapamil (VRP) did not affect CH-11-mediated apoptosis in KBv200 cells. Expression of P-glycoprotein does not induce resistance to caspase-8 and -3 activation or anti-Fas-induced cell apoptosis.
Chun-hua LING Shi-ying Zheng Dong Jiang Jin-feng Ge
Department of Medicine, The First Affiliated Hospital of Suzhou University ,Suzhou, Jiangsu, 215006, Department of Cardio-Thoracic Surgery, The First Affiliated Hospital of Suzhou University，Suzhou,215
国际会议
成都
英文
1-5
2010-06-18（万方平台首次上网日期，不代表论文的发表时间）