title: Recombinant human interleukin 24 reverses Adriamycin resistance in a human breast cancer cell line.
abstract: BACKGROUND
  The major cause of multidrug resistance is over-expression of membrane P-glycoprotein (P-gp). We investigated the effect of recombinant human interleukin 24 (rhIL-24) on the Adriamycin (ADM)-resistant human breast cancer cell line MCF-7/ADM.
  
  
  METHODS
  The cytotoxicity of rhIL-24 and ADM was determined by 3-[4,5-dimethylthiazol-2-yl], 5-diphenyl tetrazolium bromide (MTT) assays. The expression of P-gp was assessed by confocal microscopy and Western blot analysis.
  
  
  RESULTS
  The IC50 values for rhIL-24 in MCF-7/wild-type and MCF-7/ADM cells were 0.17 and 14.6 μM, respectively. The IC50 value of Adriamycin in MCF-7/ADM cells decreased in a dose-dependent manner when rhIL-24 was used. The resistance modulating factor (RMF) was directly proportional to the dose of rhIL24. ADM accumulation increased while P-gp expression decreased at a low dose (4 μM) of rhIL24 in MCF-7/ADM cells. The expression of P-gp was decreased at 4 μM in confocal microscopy and western blot analysis.
  
  
  CONCLUSIONS
  rhIL-24 circumvented the drug-resistance of MCF-7/ADM cells via activation of the transcription factor Stat 3. rhIl24 has potential to act as a P-gp inhibitor to reverse Adriamycin resistance in breast cancer.
authors.affiliation: Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, PR China. Electronic address: imranamirzada@gmail.com.
authors.forename: Muhammad Imran
authors.initials: MI
authors.lastname: Amirzada
authors.affiliation: School of Pharmaceutical Sciences, Jiangnan University, Wuxi, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Ma
authors.affiliation: School of Pharmaceutical Sciences, Jiangnan University, Wuxi, PR China.
authors.forename: Xiaohai
authors.initials: X
authors.lastname: Gong
authors.affiliation: School of Pharmaceutical Sciences, Jiangnan University, Wuxi, PR China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Faculty of Pharmacy, University of Sargodha, Sargodha, Pakistan.
authors.forename: Sajid
authors.initials: S
authors.lastname: Bashir
authors.affiliation: School of Pharmaceutical Sciences, Jiangnan University, Wuxi, PR China; Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, PR China. Electronic address: jinjian31@126.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Jin
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000235:genetics; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D007378:Interleukins / Q000008:administration & dosage / Q000494:pharmacology*; D061986:MCF-7 Cells; D018613:Microscopy, Confocal; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D050796:STAT3 Transcription Factor / Q000378:metabolism; D000099180:Interleukin-24
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin; D007378:Interleukins; D011994:Recombinant Proteins; D050796:STAT3 Transcription Factor; D000099180:Interleukin-24; C494086:STAT3 protein, human
keywords: Drug resistance; Interleukin 24; MCF-7/ADM cells; Stat 3