title: [Effect of quercetin on doxorubicin-induced expression of MDR1 gene in HL-60 cells].
abstract: OBJECTIVE
  Leukemia cells can acquire a multidrug resistant (MDR) phenotype in response to a wide variety of chemotherapeutic agents including doxorubicin (Dox). In addition to the constitutive expression in the leukemia prior to chemotherapy, a complex phenotype of pleiotropic resistance is presented in the residual or recurrent leukemia. Recent studies showed Dox-induced coexpression of COX2 and MDR1 genes in human leukaemia cells, and whether Dox-induced MDR1 up-regulation in acute leukaemia cells is dependent on COX2-transcriptional activity and thus might be overcome or prevented with COX2-promotor inhibitor quercetin interfering with COX2 expression and activity. This study was purposed to investigate the impacts of quercetin on Dox-induced mRNA expression of MDR1 and COX2 genes in HL-60 leukemia cells.
  
  
  METHODS
  The MDR1 and COX2 mRNA expression in HL-60 cells was detected by RT-PCR; the prostaglandin E2 (PGE2) release was measured by ELISA; the cytotoxicity of Dox was determined by MTT test.
  
  
  RESULTS
  The incubation of HL-60 cells with Dox not only up-regulated MDR1 mRNA, but also COX2 mRNA expression, and after co-incubation with quercetin or celecoxib, Dox-induced overexpression of MDR1 and COX2 mRNA were reduced by quercetin, not by celecoxib, whereas PGE2 release was significantly decreased with subsequent enhancement of Dox cytotoxic efficacy by both of them.
  
  
  CONCLUSIONS
  Dox-induced MDR1 up-regulation may be dependent on COX2-transcriptional activity, not PGE2, suggesting that the existence of causal link between COX2 and MDR1 expression induced by Dox, and modulation of COX2 transcriptional expression by quercetin would not only sensitize leukemia cells to Dox, but also prevent the acquisition of MDR during chemotherapy.
authors: Department of Pediatrics, Sichuan Academy of Medical Sciences & Sichuan Provincial Peopel Hospital, Chengdu 610072, Sichuan Province, China.
authors: Hai-Lan
authors: HL
authors: He
authors: Department of Pediatrics, Sichuan Academy of Medical Sciences & Sichuan Provincial Peopel Hospital, Chengdu 610072, Sichuan Province, China.
authors: Li-Juan
authors: LJ
authors: Ji
authors: Sichuan Provincial Cancer Institute, Chengdu 610041, Sichuan Province, China.
authors: Qi-Zhi
authors: QZ
authors: Li
authors: Department of Pediatrics, Sichuan Academy of Medical Sciences & Sichuan Provincial Peopel Hospital, Chengdu 610072, Sichuan Province, China.
authors: Rong
authors: R
authors: Zhang
authors: Sichuan Provincial Cancer Institute, Chengdu 610041, Sichuan Province, China. E-mail: wesleyhuangcn2002@163.com.
authors: Jian-Ming
authors: JM
authors: Huang
authors: Department of Pediatrics, Sichuan Academy of Medical Sciences & Sichuan Provincial Peopel Hospital, Chengdu 610072, Sichuan Province, China. E-mail: ligejp2002@sina.cn.
authors: Ge
authors: G
authors: Li
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D000970:Antineoplastic Agents; D004317:Doxorubicin; D015972:Gene Expression Regulation, Neoplastic; D018922:HL-60 Cells; D006801:Humans; D011794:Quercetin; D015854:Up-Regulation
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D000970:Antineoplastic Agents; D004317:Doxorubicin; D011794:Quercetin