title: Enhanced chemosensitivity by simultaneously inhibiting cell cycle progression and promoting apoptosis of drug-resistant osteosarcoma MG63/DXR cells by targeting Cyclin D1 and Bcl-2.
abstract: OBJECTIVE
  To investigate whether the inhibition of Bcl-2 and Cyclin D1 by lentivirus-mediated RNA interference enhances doxorubicin (DXR) cytotoxicity in the drug-resistant human osteosarcoma MG63 cells.
  
  
  METHODS
  Lentivirus-mediated RNAi were used to inhibit the expression of Bcl-2 or Cyclin D1 mRNA and protein; qRT-PCR, Western blotting, Flow cytometry and MTT assays were used to detect the expression of Bcl-2 and Cyclin D1 and the sensitivity to doxorubicin of MG63/DXR.
  
  
  RESULTS
  Chronic exposure to DXR induces upregulation of oncogenic Bcl-2 and CyclinD1 in osteosarcoma MG63/DXR cells. Elevated Bax and decreased cyclin D1 was observed in Bcl-2-silenced MG63/DXR cells and decreased Bcl-2 was detected in Cyclin D1-silenced MG63/DXR cells. Individual or simultaneous silencing of Bcl-2/Cyclin D1 enhanced the cytotoxicity of DXR. Furthermore, we detected a synergistic effect of enhanced chemosensitivity by co- silencing Cyclin D1 and Bcl-2.
  
  
  CONCLUSIONS
  Lentiviral RNAi targeting of Bcl-2 and Cyclin D1 simultaneously could be a potentially more effective therapeutic strategy for osteosarcomas to overcome chemoresistance.
authors.affiliation: Department of Orthopaedic Surgery, The Sixth People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai, China. shzhangchunlin@gmail.com
authors.forename: Chunlin
authors.initials: C
authors.lastname: Zhang
authors.forename: Yao
authors.initials: Y
authors.lastname: Zhao
authors.forename: Bingfang
authors.initials: B
authors.lastname: Zeng
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism*; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D005822:Genetic Vectors; D006801:Humans; D020128:Inhibitory Concentration 50; D016086:Lentivirus / Q000235:genetics; D012516:Osteosarcoma; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D000903:Antibiotics, Antineoplastic; C530104:CCND1 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D019938:Cyclin D1; D004317:Doxorubicin