title: Simultaneous suppression of Src and signal transducer and activator of transcription 3 inhibits the growth of epithelial ovarian cancer cells.
abstract: OBJECTIVE
  The reciprocal regulation of c-Src and STAT3 activation seems to be associated with the poor response to c-Src inhibitors of ovarian cancer. This study aims to investigate inhibition of cell proliferation and enhancement of the cytotoxic effect of chemotherapeutic agents via simultaneous suppression of c-Src and STAT3 in ovarian cancer cell lines.
  
  
  METHODS
  Specific siRNAs targeting c-Src and STAT3 were produced and transfected into an SKOV3 ovarian cancer cell line. We confirmed the downregulation of c-Src and STAT3 mRNAs by reverse transcriptase polymerase chain reaction. MTT assay was used to assess cytotoxicity following cisplatin administration. Protein expression level was evaluated by Western blot.
  
  
  RESULTS
  Cell growth was significantly inhibited by c-Src or STAT3 siRNA. Cytotoxicity was not increased in cisplatin-treated SKOV3 by c-Src siRNA only or STAT3 siRNA only, but cell viability was decreased significantly in cisplatin-treated cells after simultaneous transfection with c-Src and STAT3 siRNAs. Specifically, the viability was significantly decreased from 30% to 55% within the IC50 concentration following simultaneous transfection with c-Src and STAT3 siRNAs, particularly after 72 h. Src and survivin protein expression level was significantly decreased at 72 h after transfection of c-Src and STAT3 siRNAs.
  
  
  CONCLUSIONS
  This study has demonstrated the principle that the simultaneous suppression of c-Src and STAT3 inhibits the growth of epithelial ovarian cancer cells and seems to enhance the cytotoxicity of chemotherapeutic agents in ovarian cancer.
authors: Department of Obstetrics and Gynecology, University of Ulsan, Asan Medical Center, Seoul 138-736, Republic of Korea.
authors: Shin-Wha
authors: SW
authors: Lee
authors: Jin
authors: J
authors: Yoo
authors: Soo-Hyoung
authors: SH
authors: Lee
authors: Dongho
authors: D
authors: Kim
authors: Yong-Man
authors: YM
authors: Kim
authors: Young-Tak
authors: YT
authors: Kim
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000081247:CSK Tyrosine-Protein Kinase; D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects*; D002945:Cisplatin / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000096:biosynthesis; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy*; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D034741:RNA, Small Interfering / Q000494:pharmacology; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors*; D000077022:Survivin; D014162:Transfection; D019061:src-Family Kinases / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; D000077022:Survivin; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; C000631346:CSK protein, human; D002945:Cisplatin