title: Modulation of drug resistance in ovarian cancer cells by inhibition of protein kinase C-alpha (PKC-α) with small interference RNA (siRNA) agents.
abstract: OBJECTIVE
  To determine whether silence of PKC-α expression by small interference RNA (siRNA) might regulate MDR1 expression and reverse chemoresistance of ovarian cancer.
  
  
  METHODS
  We measured gene and protein expression of MDR1 and PKC-α in ovarian cancer cells and assessed their correlation with cell drug resistance. We also examined whether blocking PKC-α by RNA interference (RNAi) affected MDR1 expression and reversed drug resistance in drug sensitivity tests.
  
  
  RESULTS
  The drug resistance cell lines, OV1228/DDP and OV1228/Taxol, had higher gene and protein expression of MDR1 and PKC-α than their counterpart sensitive cell line, OV1228. SiRNA depressed PKC-α gene protein expression, as well as MDR1 and protein expression and improved the drug sensitivity in OV1228/DDP and OV1228/Taxol cells.
  
  
  CONCLUSIONS
  These results indicated that decreasing PKC-α expression with siRNA might be an effective method to improve drug sensitivity in drug resistant cells with elevated levels of PKC-α and MDR1. A new siRNA-based therapeutic strategy targeting PKC-α gene could be designed to overcome the chemoresistance of ovarian cancer.
authors.affiliation: Department of Gynecological Oncology Surgery, Jiangsu Cancer Hospital and Institute, Nanjing Medical University, Nanjing, China.
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Zhao
authors.forename: Heng
authors.initials: H
authors.lastname: Xu
authors.forename: Jun-Wei
authors.initials: JW
authors.lastname: Qu
authors.forename: Wan-Zhou
authors.initials: WZ
authors.lastname: Zhao
authors.forename: Yi-Bing
authors.initials: YB
authors.lastname: Zhao
authors.forename: Jin-Hua
authors.initials: JH
authors.lastname: Wang
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D051571:Protein Kinase C-alpha / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D051571:Protein Kinase C-alpha