Simultaneous suppression of multidrug resistance and antiapoptotic cellular defense induces apoptosis in chemoresistant human acute myeloid leukemia cells.
The emergence of acquired drug resistance is a major hurdle in the successful treatment of leukemia. Researches indicated that the main mechanisms of most cancers included so-called "pump" and "nonpump" resistance. We studied the mechanisms involved in the drug resistance of HL-60/ADR and found that its drug resistance was associated with the simultaneous overexpression of XIAP and MRP. We compared the reversal effects of XIAP and MRP ASO used in combination and separately. Reverse transcription-PCR and Western blot were applied to examine the changes of mRNA and protein levels, respectively. The results showed that XIAP and MRP ASO used separately could down-regulate the expression of XIAP and MRP in HL-60/ADR cells, respectively. XIAP and MRP ASO used in combination did not enhance the inhibition expression of XIAP and MRP of HL-60/ADR cells. The apoptosis of co-transfection group was significantly higher than XIAP ASO (P<0.05). The cytotoxicity was determined by MTT cell viability/proliferation assay. When used in combination the sensitivity of HL-60/ADR cells to DNR was increased significantly compared with XIAP or MRP ASO used separately (P<0.05). The results indicated that both XIAP and MRP were involved in the drug resistance mechanisms of HL-60/ADR cells. The sensitivity to DNR could be enhanced significantly when XIAP and MRP ASO used in combination.
Wang
Xiaofang
X
Department of Hematology, Cancer Hospital of Tianjin, Tianjin Medical University, Ti-Yuan-Bei, Huan-Hu-Xi-Road, Tianjin 300060, PR China.
Wang
Chun
C
Qin
You-Wen
YW
Yan
Shi-Ke
SK
Gao
Yan-Rong
YR
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D018922:HL-60 Cells / Q000187:drug effects; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000473:pathology*; D020320:Oligoribonucleotides, Antisense / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic; D020320:Oligoribonucleotides, Antisense; D012333:RNA, Messenger; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; D004317:Doxorubicin