Basic Research
Copyright ©2005 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 21, 2005; 11(23): 3544-3548
Published online Jun 21, 2005. doi: 10.3748/wjg.v11.i23.3544
P-glycoprotein is not involved in pathway of anti-Fas/Fas-induced apoptosis in KBv200 cells
Qiu-Liang Wu, Xing-Ping Wu, Yong-Ju Liang, Li-Ming Chen, Yan Ding, Li-Wu Fu
Qiu-Liang Wu, Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou 510060, Guangdong Province, China
Xing-Ping Wu, Clinical Laboratoty, Sun Yat-Sen University Cancer Center, Guangzhou 510060, Guangdong Province, China
Yong-Ju Liang, Li-Ming Chen, Yan Ding, Li-Wu Fu, Research Department, Sun Yat-Sen University Cancer Center, Guangzhou 510060, Guangdong Province, China
Author contributions: All authors contributed equally to the work.
Supported by the Natural Science Foundation of Guangdong Province, No. 021813 and National Natural Science Foundation of China, No. 30371659
Correspondence to: Professor Li-Wu Fu, Cancer Center, Sun Yat-Sen University, Guangzhou 510060, Guangdong Province, China. fulw@gzsums.edu.cn
Telephone: +86-20-873-43163 Fax: +86-20-873-43392
Received: June 15, 2004
Revised: June 16, 2004
Accepted: July 15, 2004
Published online: June 21, 2005
Abstract

AIM: To verify whether P-glycoprotein (P-gp) could induce cell resistance to apoptosis by inhibiting caspase-8 and caspase-3.

METHODS: Human KB cells, either drug-sensitive or with multidrug resistance (MDR) phenotype caused by overexpression of P-gp (KBv200 cells), were treated with anti-Fas (CH-11 monoclonal antibody) 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.

RESULTS: 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.

CONCLUSION: Expression of P-glycoprotein does not induce resistance to caspase-8 and -3 activation or anti-Fas-induced cell apoptosis.

Keywords: P-glycoprotein; Apoptosis; CH-11; Fas; Verapamil