title: Side population is increased in paclitaxel-resistant ovarian cancer cell lines regardless of resistance to cisplatin.
abstract: OBJECTIVE
  In recent years, cancer stem cells (CSCs) have been reported to be correlated with chemoresistance and may also be enriched in side populations (SPs). In this study, the relationship between resistance to paclitaxel (PTX) and cisplatin (CDDP) and side populations was examined in three parental PTX- and CDDP-sensitive ovarian cancer cell lines (2008, KF28, and TU-OM-1) and several other cell lines derived from these as well as the additional effects of interferon-alpha (INF-α).
  
  
  METHODS
  SP of three different parental cell lines and PTX- and/or CDDP-resistant cell lines derived from these was analyzed with flow cytometry. The expression of ABCB1 and ABCG2 in KF28 and its derived cell lines was examined. Additional cell-death effect of INF-α with PTX was also examined.
  
  
  RESULTS
  In the three parental cell lines and the PTX-sensitive cell lines derived from these lines, SP was very low. Conversely, in PTX-resistant cell lines, regardless of CDDP resistance, SP increased. ABCB1 was strongly expressed in the PTX-resistant cells, but not in their parental lines, which are sensitive to PTX. While INF-α showed only slight enhancement of the cell-death effect of PTX in PTX-sensitive cells, INF-α itself strongly induced apoptosis in PTX-resistant cells regardless of PTX concentration.
  
  
  CONCLUSIONS
  The SP could be correlated with resistance to PTX. SP could be a target of INF-α, and resistance to PTX might be overcome by INF-α.
authors.affiliation: Department of Obstetrics and Gynecology, St. Marianna University School of Medicine, Japan. yoichi@ks.kyorin-u.ac.jp
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Ken-Ichiro
authors.initials: K
authors.lastname: Seino
authors.forename: Shinji
authors.initials: S
authors.lastname: Hosonuma
authors.forename: Tatsuru
authors.initials: T
authors.lastname: Ohara
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Itamochi
authors.forename: Seiji
authors.initials: S
authors.lastname: Isonishi
authors.forename: Tsunekazu
authors.initials: T
authors.lastname: Kita
authors.forename: Haruka
authors.initials: H
authors.lastname: Wada
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kojo
authors.forename: Kazushige
authors.initials: K
authors.lastname: Kiguchi
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis / Q000235:genetics; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis / Q000235:genetics; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D018284:Cystadenocarcinoma, Serous / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D017239:Paclitaxel / Q000494:pharmacology*
chemical_list: C513055:ABCB1 protein, human; C116614:ABCG2 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D016898:Interferon-alpha; D009363:Neoplasm Proteins; D017239:Paclitaxel; D002945:Cisplatin