Overexpression of Survivin and XIAP in MDR cancer cells unrelated to P-glycoprotein.
Cancer cells developing multidrug resistance (MDR) is one of the most serious clinical problems responsible for the failure of cancer chemotherapy. P-glycoprotein (P-gp) overexpression and inhibitor of apoptosis proteins (IAPs) overexpression in cancer cells are the two common mechanisms of MDR. However, the relationship between IAPs and P-gp in MDR cancer cells is unknown. We investigated the expression levels of two IAPs, Survivin and XIAP, and their interaction with P-gp in MDR cancer cells. We have found that the human epidermoid carcinoma cells KBv200 and breast cancer cells MCF-7/Adr overexpress not only P-gp but also XIAP and Survivin, and showed high resistance to chemotherapeutic drugs doxorubicin, docetaxel and vincristine, in contrast to their parental cells KB and MCF-7. Furthermore, upregulation of Survivin or XIAP through transfection with the plasmid pECFPN1-Survivin or pcDNA3-6myc-XIAP in these four cell sublines did not affect the P-gp expression. Downregulation of Survivin or XIAP through transfection with the Survivin or XIAP siRNA did not have an effect on the P-gp expression in these resistant cells. Additionally, our immunoprecipitation results showed that Survivin or XIAP did not directly bind to P-gp. In summary, our study suggested that the overexpression of Survivin and XIAP in MDR cancer cells does not directly interact with P-gp.
Shi
Zhi
Z
State Key Laboratory for Oncology in South China, Cancer Center, Sun Yat-Sen University, Guangzhou 510060, P.R. China.
Liang
Yong-Ju
YJ
Chen
Zhe-Sheng
ZS
Wang
Xiao-Hong
XH
Ding
Yan
Y
Chen
Li-Ming
LM
Fu
Li-Wu
LW
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism*; D045744:Cell Line, Tumor; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D000077022:Survivin; D015854:Up-Regulation; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000235:genetics / Q000378:metabolism*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human